Home Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis
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Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis

  • Kebinuer Tuerxun , Shufang Zhang and Yuexin Zhang EMAIL logo
Published/Copyright: December 28, 2021
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Open Life Sciences
From the journal Open Life Sciences Volume 16 Issue 1

Abstract

Paired-like homeodomain 2 (PITX2) functions as a transcription factor to participate in vertebrate embryogenesis, and dysregulated PITX2 expression was associated with the progression of various cancers. The functional role of PITX2 in tumorigenesis of liver cancer remains unknown. Western blot analysis showed that expression levels of PITX2 were enhanced in the liver cancer tissues and cells. siRNAs targeting PITX2 induced downregulation of PITX2 in liver cancer cells. siRNA-induced knockdown of PITX2 decreased liver cancer cell viability and proliferation, while promoting cell apoptosis by increasing cleaved-PARP, cleaved caspase 3, and cleaved caspase 9. The knockdown of PITX2 repressed liver cancer cell migration and invasion. In conclusion, elevated PITX2 expression was associated with liver cancer progression through repression of cell apoptosis and promoting cell proliferation and metastasis, and silencing of PITX2 might serve as a potential therapeutic strategy for the treatment of liver cancer.

Keywords: PITX2; liver cancer; proliferation; metastasis

1 Introduction

Liver cancer is the fifth most common cancer globally and the third leading cause of cancer-related mortality with increasing incidence and occurrence [1]. Alcohol, hepatitis B virus, or hepatitis C virus often induce cirrhosis and result in liver cancer, and antiviral therapy reduces the risk of liver cancer [2]. For example, medical herbs that reduced oxidative stress, suppressed inflammatory response, induced apoptosis, and protected hepatocytes from cirrhosis [3] were widely used in the treatment of liver cancer [4]. However, despite recent advances in the diagnosis and treatment of liver cancer, the long-term prognosis for the patients remains poor [5]. For patients with advanced liver cancer, the overall 5-year survival is only 5%, mainly due to intrahepatic recurrence and metastasis [6]. Therefore, exploring the molecular mechanism of liver cancer progression and metastasis is of clinical significance and would improve the prognosis of the patients.

Paired-like homeodomain 2 (PITX2), which plays an important role in cell proliferation and differentiation, is involved in the development of eyes, teeth, and abdominal organs [7]. Increasing evidence has shown the key role of PITX2 in tumorigenesis. For example, enforced PITX2 expression in ovarian cancer cells enhanced proteins involved in cell cycle regulation, such as Cyclin D1 and c-myc, to promote cell proliferation and growth [8]. PITX2 transcriptionally activated ATP binding cassette subfamily B member 1, a multidrug transporter, to protect against doxorubicin toxicity in renal cancer cell lines [9]. PITX2 also transcriptionally regulated interferon-inducible transmembrane protein 1 to promote the letrozole resistance in breast cancer cells [10]. In addition to the tumor promotive role, PITX2 also functioned as a poor prognostic biomarker for breast cancer [11], colorectal carcinoma [12], head and neck squamous cell carcinoma [13], and esophageal squamous cell carcinoma [14]. However, the functional role and mechanism of PITX2 in liver cancer have not been reported yet.

This study first aimed to investigate the expression levels of PITX2 in liver cancer tissues and cells. The effects of PITX2 on the proliferation, migration, invasion, and apoptosis of liver cancer cells were then assessed. The investigation of the relevant mechanisms involved in PITX2-mediated liver cancer progression provided a theoretical basis for the search and development of new targets for the diagnosis and treatment of liver cancer.

2 Materials and methods

2.1 Tissue samples

Forty pairs of liver cancer tissues and the adjacent normal liver tissues were acquired from patients recruited in the First Affiliated Hospital of Xinjiang Medical University. The clinicopathological data for patients are shown in Table 1.

Table 1

Correlation/association between PITX2 expression and clinicopathological features

PITX2 Fisher/X 2 p
Clinical features High (n = 20) Low (n = 20)
Age >60 8 6 0.440 0.507
≤60 12 14
Gender Male 14 13 0.114 0.736
Female 6 7
Tumor size >5 cm 6 5 0.125 0.723
≤5 cm 14 15
Clinical stages I–II 4 11 5.227 0.022
III–IV 16 9
Metastasis status Yes 13 5 6.465 0.011
No 7 15

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University.

2.2 Cell culture and transfection

Liver cancer cells (Hep3B, MHCC-97H, Huh7, and HCCLM3) and human fetal hepatocyte line (L-02) were purchased from the ATCC (Manassas, VA, USA). Cells were grown in DMEM medium (Gibco BRL, Gaithersburg, MD, USA) containing 10% fetal bovine serum (Gibco BRL).

siRNA targeting PITX2 (si-PITX2-1#: 5′-CAGCCUGAAUAACUUGAACT T-3′ and si-PITX2-2#: 5′-GCCGACTCCTCCGTATGTTTA-3′) and the negative control (si-NC 5′-UUCUCCGAACGUGUCACGUTT-3′) were synthesized in RiboBio (Guangzhou, China). Huh7 was plated in a 96-well plate and transfected with 20 nM siRNAs by Lipofectamine 2000 (Thermo Fisher Scientific, Waltham, MA, USA), and the cells were used for functional assays 2 days post-transfection according to previous research [15].

2.3 Cell viability and proliferation

Huh7 (1 × 103 cells/well) cells were plated in a 96-well plate and then indicated transfections were performed. Cells were cultured in the plate for 1, 2, 3, or 4 days. A total of 0.5 mg/mL MTT solution (Sigma-Aldrich, St. Louis, MO, USA) was added to each well and incubated with the cells for 3 h. Lysis buffer (10% SDS in 0.01 M HCl) was added, and the absorbance at 450 nm in each well was measured by Spectrometer (Thermo Fisher Scientific). Huh7 (1 × 103 cells/well) cells were plated in a 6-well plate and then performed with indicated transfections. Cells were cultured for 2 weeks. Fixed cells were stained with 0.4% crystal violet (Sigma-Aldrich), and the colonies were measured under a light microscope (Olympus Corp. Tokyo, Japan) according to previous research [15].

2.4 Cell apoptosis

Huh7 was plated in a 6-well plate and then performed with indicated transfections. Cells (1 × 106 cells) were treated with trypsin and resuspended in 100 µL of Annexin V‑binding buffer (Thermo Fisher Scientific) and then incubated with 5 µL of Annexin V-FITC (Thermo Fisher Scientific) for 15 min. A total of 400 µL of Annexin V-binding buffer containing 2 µL of propidium iodide solution (2 mg/mL) was used to incubate the cells. Attune™ Flow Cytometer (Thermo Fisher Scientific) was used to detect the cell apoptosis rate according to previous research [16].

2.5 Cell migration and invasion

Huh7 (5 × 103 cells/well) was plated in a 6-well plate and then performed with indicated transfections. Scratch wounds were generated in the monolayer of cells in each well via a pipette tip. The wounds were calculated under the light microscope (Olympus) 24 h later. Huh7 with indicated transfections (1 × 105 cells) in 200 μL of serum-free DMEM medium were plated in the upper chamber of Matrigel-coated well (24-well, Corning, Tewksbury, MA, USA). A total of 400 µL of DMEM containing 10% fetal bovine serum was added to the lower chamber. Cells in the lower chamber were stained with 1% crystal violet 24 h later before being counted under the microscope (Olympus), according to previous research [17].

2.6 Western blot

Proteins were extracted from liver cancer tissues or cells via RIPA Lysis and Extraction Buffer (Thermo Fisher Scientific), and the protein concentrations were assessed by an acid protein kit (Thermo Fisher Scientific). Proteins were separated by sodium dodecyl sulfate-polyacrylamide gel and electro-transferred onto PVDF membrane (Millipore, Bedford, MA, USA) before blocking with 5% BSA. The membranes were then incubated overnight with primary antibodies: anti-PITX2, anti-cleaved-PARP (1:2,000, Cell Signaling, Beverly, MA, USA), cleaved caspase 3/9, and anti-cleaved caspase 3/9 (1:2,500, Cell Signaling), and anti-GAPDH (1:4,000, Cell Signaling). The membranes were incubated with corresponding horseradish peroxidase-labeled secondary antibody (1:5,000; Cell Signaling) before detection of the immunoreactivities of the bands in the membranes via enhanced chemiluminescence (KeyGen, Nanjing, China) according to previous research [16].

2.7 Statistical analysis

Data were expressed as mean value ± SEM, and performed with one-way analysis of variance or student’s t test under GraphPad Prism software. The p value < 0.05 was considered as statistically significant.

3 Results

3.1 Elevated PITX2 in liver cancer

A total of 40 pairs of liver cancer and the adjacent liver tissues were collected and applied for western blot analysis to determine the expression level of PITX2 in liver cancer. The result showed that PITX2 was elevated in the liver cancer tissues compared with the adjacent normal tissues (Figure 1a). Analysis of the relationship between PITX2 expression and clinicopathological features of the patients showed that high PITX2 expression was significantly associated with the patients’ clinical stages and metastasis status (Table 1). Moreover, liver cancer cells (Hep3B, MHCC-97H, Huh7, and HCCLM3) showed increased expression of PITX2 compared with the human fetal hepatocyte line (L-02) (Figure 1b), suggesting that elevated PITX2 might be involved in liver cancer progression.

Figure 1 Elevated PITX2 in liver cancer. (a) Protein expression of PITX2 was elevated in liver cancer tissues compared to the adjacent liver tissues. (b) Protein expression of PITX2 was elevated in liver cancer cells (Hep3B, MHCC-97H, Huh7, and HCCLM3) compared to human fetal hepatocyte line (L-02). N = 3. **p < 0.01.
Figure 1

Elevated PITX2 in liver cancer. (a) Protein expression of PITX2 was elevated in liver cancer tissues compared to the adjacent liver tissues. (b) Protein expression of PITX2 was elevated in liver cancer cells (Hep3B, MHCC-97H, Huh7, and HCCLM3) compared to human fetal hepatocyte line (L-02). N = 3. **p < 0.01.

3.2 Silence of PITX2 repressed liver cancer cell proliferation

A loss of function assay through siRNA-mediated knockdown of PITX2 was applied to investigate the effect of PITX2 on liver cancer cell proliferation. Transfection with siPITX2 in Huh7 showed lower protein expression of PITX2 than the control cells or cells transfected with siNC (Figure 2a). The stability of the PITX2 knockdown is shown in Appendix Figure A1. Huh7 cells transfected with siPITX2 showed lower cell viability than the control or cells transfected with siNC (Figure 2b). Moreover, cell proliferation of Huh7 was repressed by siPITX2 transfection as demonstrated by lower colony numbers in cells transfected with siPITX2 than cells transfected with siNC or control (Figure 2c). These results demonstrated the anti-proliferative role of PITX2 silencing on liver cancer cells.

Figure 2 Silence of PITX2 repressed liver cancer cell proliferation. (a) Transfection with siPITX2 decreased protein expression of PITX2 in Huh7. N = 3. (b) Transfection with siPITX2 decreased cell viability of Huh7. N = 3. (c) Transfection with siPITX2 decreased cell proliferation of Huh7. N = 3. *p < 0.05, **p < 0.01.
Figure 2

Silence of PITX2 repressed liver cancer cell proliferation. (a) Transfection with siPITX2 decreased protein expression of PITX2 in Huh7. N = 3. (b) Transfection with siPITX2 decreased cell viability of Huh7. N = 3. (c) Transfection with siPITX2 decreased cell proliferation of Huh7. N = 3. *p < 0.05, **p < 0.01.

3.3 Silence of PITX2 repressed liver cancer cell migration and invasion

The effect of PITX2 on liver cancer cell invasion was then assessed by wound healing and transwell assays. Results revealed that siRNA-mediated knockdown of PITX2 repressed cell migration of Huh7 (Figure 3a). Moreover, the cell invasion of Huh7 was also retarded by the knockdown of PITX2 (Figure 3b), suggesting the anti-invasive effect of PITX2 silencing on liver cancer cells.

Figure 3 Silence of PITX2 repressed liver cancer cell migration and invasion. (a) Transfection with siPITX2 decreased cell migration of Huh7. N = 3. (b) Transfection with siPITX2 decreased cell invasion of Huh7. N = 3. **p < 0.01.
Figure 3

Silence of PITX2 repressed liver cancer cell migration and invasion. (a) Transfection with siPITX2 decreased cell migration of Huh7. N = 3. (b) Transfection with siPITX2 decreased cell invasion of Huh7. N = 3. **p < 0.01.

3.4 Silence of PITX2-promoted liver cancer cell apoptosis

In addition to the anti-proliferative and anti-invasive effects of PITX2 silence on liver cancer cells, the effect of PITX2 on liver cancer cell apoptosis was also assessed by flow cytometry and western blot assays. The result indicated that siRNA-mediated knockdown of PITX2 promoted the cell apoptosis of Huh7 (Figure 4a). Moreover, protein expression of cleaved-PARP, cleaved caspase 3, and cleaved caspase 9 in Huh7 were increased by knockdown of PITX2 (Figure 4b), suggesting the anti-apoptotic effect of PITX2 on liver cancer cells.

Figure 4 Silence of PITX2 promoted liver cancer cell apoptosis. (a) Transfection with siPITX2 promoted cell apoptosis of Huh7. N = 3. (b) Transfection with siPITX2 increased protein expression of cleaved-PARP, cleaved caspase 3, and cleaved caspase 9 in Huh7. N = 3. *p < 0.05, **p < 0.01.
Figure 4

Silence of PITX2 promoted liver cancer cell apoptosis. (a) Transfection with siPITX2 promoted cell apoptosis of Huh7. N = 3. (b) Transfection with siPITX2 increased protein expression of cleaved-PARP, cleaved caspase 3, and cleaved caspase 9 in Huh7. N = 3. *p < 0.05, **p < 0.01.

4 Discussion

Transcription factors encoded by homeobox genes are implicated in cell differentiation and participate in embryonic development [18]. The association between homeobox transcription factors and tumorigenesis has been widely investigated in recent research [18]. Hlx, Hex, and prospero-related homeobox 1 genes were reported to be involved in liver bud development [19]. Prospero-related homeobox 1 has been shown to repress hepatocellular carcinoma cell proliferation [20]. Bicoid-related PITX genes are shown to be responsible for cell survival [21], and PITX1 functioned as a tumor suppressor in hepatocarcinogenesis [22]. Since PITX2 has been reported to be involved in tumorigenesis of various tumors, the involvement of PITX2 in liver cancer was investigated in this study.

First, our results showed that PITX2 was elevated in the liver cancer tissues and cells. The diagnostic or prognostic roles of PITX2 in breast cancer [11], colorectal carcinoma [12], head and neck squamous cell carcinoma [13], and esophageal squamous cell carcinoma [14] have been reported before. The association between PITX2 expression and clinicopathological features of patients with liver cancer should be investigated in further research to explore its diagnostic or prognostic roles in liver cancer.

Second, the functional assays in this study identified the promoting role of PITX2 in liver cancer progression. Silencing of PITX2 reduced cell viability of liver cancer cells, repressed cell proliferation, migration, and invasion, and promoted cell apoptosis. Almost 80% of PITX2 expression was reduced by transfection with si-PITX2-1# or 2#, suggesting that other homeobox transcriptional factors might also be implicated in the pathogenesis of liver cancer. Moreover, the epithelial-mesenchymal transition has been shown to be involved in liver cancer invasion and metastasis [23], and over-expression of PITX2 contributed to the gain of mesenchymal markers and loss of epithelial markers to promote epithelial-mesenchymal transition of ovarian cancer [24]. The effect of PITX2 on epithelial-mesenchymal transition of liver cancer should be investigated to confirm the promoting role of PITX2 on liver cancer metastasis.

Aberrant activation of Wnt/β-catenin participates in tumor cell proliferation, migration, invasion, differentiation, and apoptosis [25], and inhibitors of the Wnt/β-catenin pathway have been applied in clinical trials for drug therapy of tumors [25]. Alcohol, hepatitis B virus, or hepatitis C virus could induce activation of Wnt/β-catenin in hepatic precancerous lesions and cancerous foci [26]. Inhibitors targeting Wnt/β-catenin signaling have been preclinically and clinically evaluated in liver cancers [27]. PITX2 was reported to be a Wnt signaling target gene and contributed to metastatic prostate cancer [28]. Moreover, PITX2 has been shown to interact with Wnt genes involved in canonical, noncanonical, or other pathways, such as WNT2/5A/9A/6/2B, to promote ovarian adenocarcinoma cell proliferation [29]. Activation of the Wnt/β-catenin signaling pathway by PITX2 contributed to lung adenocarcinoma progression [30]. Therefore, PITX2 might contribute to liver cancer progression through activation of the Wnt/β-catenin signaling pathway. However, the in vivo animal model should be used to assess the effects of PITX2 on liver cancer cell growth.

In summary, this study demonstrated the protective effect of PITX2 silencing on liver cancer cell proliferation, migration, and invasion. This study might provide a novel therapeutic target for the treatment of liver cancer.

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Appendix

Figure A1 The stability of si-PITX2-#1 (a) and si-PITX2-#2 (b) transfection in Huh7. N = 3. **p < 0.01.
Figure A1

The stability of si-PITX2-#1 (a) and si-PITX2-#2 (b) transfection in Huh7. N = 3. **p < 0.01.

  1. Funding information: The authors state no funding involved.

  2. Author contributions: Kebinuer Tuerxun designed the study and supervised the data collection; Shufang Zhang analyzed the data and interpreted the data; Kebinuer Tuerxun and Shufang Zhang prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2021-03-15
Revised: 2021-09-01
Accepted: 2021-09-21
Published Online: 2021-12-28

© 2021 Kebinuer Tuerxun et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  45. Long noncoding RNA HULC contributes to paclitaxel resistance in ovarian cancer via miR-137/ITGB8 axis
  46. Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress
  47. Prognostic value of the neutrophil-to-lymphocyte ratio in acute organophosphorus pesticide poisoning
  48. Gastroprotective effects of diosgenin against HCl/ethanol-induced gastric mucosal injury through suppression of NF-κβ and myeloperoxidase activities
  49. Silencing of LINC00707 suppresses cell proliferation, migration, and invasion of osteosarcoma cells by modulating miR-338-3p/AHSA1 axis
  50. Successful extracorporeal membrane oxygenation resuscitation of patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism: A case report
  51. Effects of miR-185-5p on replication of hepatitis C virus
  52. Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
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  54. Multimodal magnetic resonance imaging analysis in the characteristics of Wilson’s disease: A case report and literature review
  55. Therapeutic potential of anticoagulant therapy in association with cytokine storm inhibition in severe cases of COVID-19: A case report
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  57. Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
  58. Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
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  60. Clonal diversity of the B cell receptor repertoire in patients with coronary in-stent restenosis and type 2 diabetes
  61. CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression
  62. WDR74 promotes proliferation and metastasis in colorectal cancer cells through regulating the Wnt/β-catenin signaling pathway
  63. Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis
  64. Curcumin suppresses the progression of gastric cancer by regulating circ_0056618/miR-194-5p axis
  65. Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway
  66. lncRNA NEAT1 regulates CYP1A2 and influences steroid-induced necrosis
  67. A two-microRNA signature predicts the progression of male thyroid cancer
  68. Isolation of microglia from retinas of chronic ocular hypertensive rats
  69. Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study
  70. Calcineurin Aβ gene knockdown inhibits transient outward potassium current ion channel remodeling in hypertrophic ventricular myocyte
  71. Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
  72. Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer
  73. circ_CHFR regulates ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by miR-15a-5p/EGFR axis in human brain microvessel endothelial cells
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  75. Ubiquitin-conjugating enzyme E2T promotes tumor stem cell characteristics and migration of cervical cancer cells by regulating the GRP78/FAK pathway
  76. Carriage of HLA-DRB1*11 and 1*12 alleles and risk factors in patients with breast cancer in Burkina Faso
  77. Protective effect of Lactobacillus-containing probiotics on intestinal mucosa of rats experiencing traumatic hemorrhagic shock
  78. Glucocorticoids induce osteonecrosis of the femoral head through the Hippo signaling pathway
  79. Endothelial cell-derived SSAO can increase MLC20 phosphorylation in VSMCs
  80. Downregulation of STOX1 is a novel prognostic biomarker for glioma patients
  81. miR-378a-3p regulates glioma cell chemosensitivity to cisplatin through IGF1R
  82. The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats
  83. TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ
  84. The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
  85. Red blood cell distribution width-standard deviation but not red blood cell distribution width-coefficient of variation as a potential index for the diagnosis of iron-deficiency anemia in mid-pregnancy women
  86. Small cell neuroendocrine carcinoma expressing alpha fetoprotein in the endometrium
  87. Superoxide dismutase and the sigma1 receptor as key elements of the antioxidant system in human gastrointestinal tract cancers
  88. Molecular characterization and phylogenetic studies of Echinococcus granulosus and Taenia multiceps coenurus cysts in slaughtered sheep in Saudi Arabia
  89. ITGB5 mutation discovered in a Chinese family with blepharophimosis-ptosis-epicanthus inversus syndrome
  90. ACTB and GAPDH appear at multiple SDS-PAGE positions, thus not suitable as reference genes for determining protein loading in techniques like Western blotting
  91. Facilitation of mouse skin-derived precursor growth and yield by optimizing plating density
  92. 3,4-Dihydroxyphenylethanol ameliorates lipopolysaccharide-induced septic cardiac injury in a murine model
  93. Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis
  94. Expression of CDK9 in endometrial cancer tissues and its effect on the proliferation of HEC-1B
  95. Novel predictor of the occurrence of DKA in T1DM patients without infection: A combination of neutrophil/lymphocyte ratio and white blood cells
  96. Investigation of molecular regulation mechanism under the pathophysiology of subarachnoid hemorrhage
  97. miR-25-3p protects renal tubular epithelial cells from apoptosis induced by renal IRI by targeting DKK3
  98. Bioengineering and Biotechnology
  99. Green fabrication of Co and Co3O4 nanoparticles and their biomedical applications: A review
  100. Agriculture
  101. Effects of inorganic and organic selenium sources on the growth performance of broilers in China: A meta-analysis
  102. Crop-livestock integration practices, knowledge, and attitudes among smallholder farmers: Hedging against climate change-induced shocks in semi-arid Zimbabwe
  103. Food Science and Nutrition
  104. Effect of food processing on the antioxidant activity of flavones from Polygonatum odoratum (Mill.) Druce
  105. Vitamin D and iodine status was associated with the risk and complication of type 2 diabetes mellitus in China
  106. Diversity of microbiota in Slovak summer ewes’ cheese “Bryndza”
  107. Comparison between voltammetric detection methods for abalone-flavoring liquid
  108. Composition of low-molecular-weight glutenin subunits in common wheat (Triticum aestivum L.) and their effects on the rheological properties of dough
  109. Application of culture, PCR, and PacBio sequencing for determination of microbial composition of milk from subclinical mastitis dairy cows of smallholder farms
  110. Investigating microplastics and potentially toxic elements contamination in canned Tuna, Salmon, and Sardine fishes from Taif markets, KSA
  111. From bench to bar side: Evaluating the red wine storage lesion
  112. Establishment of an iodine model for prevention of iodine-excess-induced thyroid dysfunction in pregnant women
  113. Plant Sciences
  114. Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose
  115. Comparative analysis of the SPL gene family in five Rosaceae species: Fragaria vesca, Malus domestica, Prunus persica, Rubus occidentalis, and Pyrus pyrifolia
  116. Identification of leaf rust resistance genes Lr34 and Lr46 in common wheat (Triticum aestivum L. ssp. aestivum) lines of different origin using multiplex PCR
  117. Investigation of bioactivities of Taxus chinensis, Taxus cuspidata, and Taxus × media by gas chromatography-mass spectrometry
  118. Morphological structures and histochemistry of roots and shoots in Myricaria laxiflora (Tamaricaceae)
  119. Transcriptome analysis of resistance mechanism to potato wart disease
  120. In silico analysis of glycosyltransferase 2 family genes in duckweed (Spirodela polyrhiza) and its role in salt stress tolerance
  121. Comparative study on growth traits and ions regulation of zoysiagrasses under varied salinity treatments
  122. Role of MS1 homolog Ntms1 gene of tobacco infertility
  123. Biological characteristics and fungicide sensitivity of Pyricularia variabilis
  124. In silico/computational analysis of mevalonate pyrophosphate decarboxylase gene families in Campanulids
  125. Identification of novel drought-responsive miRNA regulatory network of drought stress response in common vetch (Vicia sativa)
  126. How photoautotrophy, photomixotrophy, and ventilation affect the stomata and fluorescence emission of pistachios rootstock?
  127. Apoplastic histochemical features of plant root walls that may facilitate ion uptake and retention
  128. Ecology and Environmental Sciences
  129. The impact of sewage sludge on the fungal communities in the rhizosphere and roots of barley and on barley yield
  130. Domestication of wild animals may provide a springboard for rapid variation of coronavirus
  131. Response of benthic invertebrate assemblages to seasonal and habitat condition in the Wewe River, Ashanti region (Ghana)
  132. Molecular record for the first authentication of Isaria cicadae from Vietnam
  133. Twig biomass allocation of Betula platyphylla in different habitats in Wudalianchi Volcano, northeast China
  134. Animal Sciences
  135. Supplementation of probiotics in water beneficial growth performance, carcass traits, immune function, and antioxidant capacity in broiler chickens
  136. Predators of the giant pine scale, Marchalina hellenica (Gennadius 1883; Hemiptera: Marchalinidae), out of its natural range in Turkey
  137. Honey in wound healing: An updated review
  138. NONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block
  139. Radiotherapy for the treatment of pulmonary hydatidosis in sheep
  140. Retraction
  141. Retraction of “Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating microRNA-34a-5p/NOTCH1 signaling pathway”
  142. Special Issue on Reuse of Agro-Industrial By-Products
  143. An effect of positional isomerism of benzoic acid derivatives on antibacterial activity against Escherichia coli
  144. Special Issue on Computing and Artificial Techniques for Life Science Applications - Part II
  145. Relationship of Gensini score with retinal vessel diameter and arteriovenous ratio in senile CHD
  146. Effects of different enantiomers of amlodipine on lipid profiles and vasomotor factors in atherosclerotic rabbits
  147. Establishment of the New Zealand white rabbit animal model of fatty keratopathy associated with corneal neovascularization
  148. lncRNA MALAT1/miR-143 axis is a potential biomarker for in-stent restenosis and is involved in the multiplication of vascular smooth muscle cells
https://doi.org/10.1515/biol-2021-0133
Keywords for this article
PITX2; liver cancer; proliferation; metastasis
Creative Commons
BY 4.0

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  83. TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ
  84. The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
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  87. Superoxide dismutase and the sigma1 receptor as key elements of the antioxidant system in human gastrointestinal tract cancers
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  93. Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis
  94. Expression of CDK9 in endometrial cancer tissues and its effect on the proliferation of HEC-1B
  95. Novel predictor of the occurrence of DKA in T1DM patients without infection: A combination of neutrophil/lymphocyte ratio and white blood cells
  96. Investigation of molecular regulation mechanism under the pathophysiology of subarachnoid hemorrhage
  97. miR-25-3p protects renal tubular epithelial cells from apoptosis induced by renal IRI by targeting DKK3
  98. Bioengineering and Biotechnology
  99. Green fabrication of Co and Co3O4 nanoparticles and their biomedical applications: A review
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  104. Effect of food processing on the antioxidant activity of flavones from Polygonatum odoratum (Mill.) Druce
  105. Vitamin D and iodine status was associated with the risk and complication of type 2 diabetes mellitus in China
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  107. Comparison between voltammetric detection methods for abalone-flavoring liquid
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  109. Application of culture, PCR, and PacBio sequencing for determination of microbial composition of milk from subclinical mastitis dairy cows of smallholder farms
  110. Investigating microplastics and potentially toxic elements contamination in canned Tuna, Salmon, and Sardine fishes from Taif markets, KSA
  111. From bench to bar side: Evaluating the red wine storage lesion
  112. Establishment of an iodine model for prevention of iodine-excess-induced thyroid dysfunction in pregnant women
  113. Plant Sciences
  114. Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose
  115. Comparative analysis of the SPL gene family in five Rosaceae species: Fragaria vesca, Malus domestica, Prunus persica, Rubus occidentalis, and Pyrus pyrifolia
  116. Identification of leaf rust resistance genes Lr34 and Lr46 in common wheat (Triticum aestivum L. ssp. aestivum) lines of different origin using multiplex PCR
  117. Investigation of bioactivities of Taxus chinensis, Taxus cuspidata, and Taxus × media by gas chromatography-mass spectrometry
  118. Morphological structures and histochemistry of roots and shoots in Myricaria laxiflora (Tamaricaceae)
  119. Transcriptome analysis of resistance mechanism to potato wart disease
  120. In silico analysis of glycosyltransferase 2 family genes in duckweed (Spirodela polyrhiza) and its role in salt stress tolerance
  121. Comparative study on growth traits and ions regulation of zoysiagrasses under varied salinity treatments
  122. Role of MS1 homolog Ntms1 gene of tobacco infertility
  123. Biological characteristics and fungicide sensitivity of Pyricularia variabilis
  124. In silico/computational analysis of mevalonate pyrophosphate decarboxylase gene families in Campanulids
  125. Identification of novel drought-responsive miRNA regulatory network of drought stress response in common vetch (Vicia sativa)
  126. How photoautotrophy, photomixotrophy, and ventilation affect the stomata and fluorescence emission of pistachios rootstock?
  127. Apoplastic histochemical features of plant root walls that may facilitate ion uptake and retention
  128. Ecology and Environmental Sciences
  129. The impact of sewage sludge on the fungal communities in the rhizosphere and roots of barley and on barley yield
  130. Domestication of wild animals may provide a springboard for rapid variation of coronavirus
  131. Response of benthic invertebrate assemblages to seasonal and habitat condition in the Wewe River, Ashanti region (Ghana)
  132. Molecular record for the first authentication of Isaria cicadae from Vietnam
  133. Twig biomass allocation of Betula platyphylla in different habitats in Wudalianchi Volcano, northeast China
  134. Animal Sciences
  135. Supplementation of probiotics in water beneficial growth performance, carcass traits, immune function, and antioxidant capacity in broiler chickens
  136. Predators of the giant pine scale, Marchalina hellenica (Gennadius 1883; Hemiptera: Marchalinidae), out of its natural range in Turkey
  137. Honey in wound healing: An updated review
  138. NONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block
  139. Radiotherapy for the treatment of pulmonary hydatidosis in sheep
  140. Retraction
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  142. Special Issue on Reuse of Agro-Industrial By-Products
  143. An effect of positional isomerism of benzoic acid derivatives on antibacterial activity against Escherichia coli
  144. Special Issue on Computing and Artificial Techniques for Life Science Applications - Part II
  145. Relationship of Gensini score with retinal vessel diameter and arteriovenous ratio in senile CHD
  146. Effects of different enantiomers of amlodipine on lipid profiles and vasomotor factors in atherosclerotic rabbits
  147. Establishment of the New Zealand white rabbit animal model of fatty keratopathy associated with corneal neovascularization
  148. lncRNA MALAT1/miR-143 axis is a potential biomarker for in-stent restenosis and is involved in the multiplication of vascular smooth muscle cells
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