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LncRNA-p21 suppresses cell proliferation and induces apoptosis in gastric cancer by sponging miR-514b-3p and up-regulating ARHGEF9 expression

  • Xiaobin Ma , Wenyu Yan , Peng Xu , Li Ma , Ying Zan , Lanxuan Huang , Guanying Wang , Lili Liu and Wentao Hui ORCID logo EMAIL logo
Published/Copyright: August 11, 2022
Biological Chemistry
From the journal Biological Chemistry Volume 403 Issue 10

Abstract

The long non-coding RNA p21 (lncRNA-p21) was a tumor suppressor gene in most cancer types including gastric cancer (GC). We aimed to identify a specific lncRNA-p21-involved pathway in regulating the proliferation and apoptosis of GC cells. A lower lncRNA-p21 expression in tumors was associated with advanced disease stage and predicted worse survival of GC patients. LncRNA-p21 overexpression in GC cell line somatic gastric cancer (SGC)-7901 and human gastric cancer (HGC)-27 suppressed cell proliferation and enhanced apoptosis, while lncRNA-p21 knockdown caused the opposite effects. Through bioinformatics analysis and luciferase-based reporter assays, we identified miR-514b-3p as a sponge target of lncRNA-p21. Cdc42 guanine nucleotide exchange factor 9 (ARHGEF9), functioned as a tumor suppress factor in GC, was found as the downstream target of miR-514-3p, and their expressions were negatively correlated in GC tumor tissues. In addition, like lncRNA-p21 overexpression alone, miR-514-3p inactivation alone also led to decreased proliferation and increased apoptosis in SGC-7901 and HGC-27 cells, which were markedly attenuated by additional ARHGEF9 knockdown. Xenograft SGC-7901 cells with more lncRNA-p21 or ARHGEF9 expressions or with less miR-514-3p expression exhibited obviously slower in vivo growth than the control SGC-7901 cells in nude mice. Our study reveals a novel lncRNA-p21/miR-514b-3p/ARHGEF9 pathway that can be targeted for GC therapy.

Keywords: apoptosis; ARHGEF9; gastric cancer; lncRNA-p21; miR-514b-3p
Corresponding author: Wentao Hui, Department of Oncology, The Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an 710004, Shaanxi, China, E-mail:
Xiaobin Ma and Wenyu Yan contributed equally to this work.

Acknowledgments

This work was supported by grants from the International Cooperative Project of Shaanxi Province, People’s Republic of China (No. 2019KW-077, 2022KW-01).

  1. Author contributions: Xiaobin Ma, Wenyu Yan and Wentao Hui conceived and designed the experiments. Li Ma, Peng Xu, and Ying Zan performed the experiments. Li Ma, Ying Zan, Lanxuan Huang, Guanying Wang, Lili Liu and Wentao Hui analyzed and interpreted the data. Xiaobin Ma and Wenyu Yan wrote the manuscript. All authors read and approved the final manuscript.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

  4. Ethics approval and consent to participate: All animal experiments were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University.

  5. Availability of data and material: The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2022-0153).

Received: 2022-04-02
Accepted: 2022-07-01
Published Online: 2022-08-11
Published in Print: 2022-09-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Research Articles/Short Communications
  3. Cell Biology and Signaling
  4. Diselenide-derivative of 3-pyridinol targets redox enzymes leading to cell cycle deregulation and apoptosis in A549 cells
  5. NF90/NFAR (nuclear factors associated with dsRNA) – a new methylation substrate of the PRMT5-WD45-RioK1 complex
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  8. LncRNA-p21 suppresses cell proliferation and induces apoptosis in gastric cancer by sponging miR-514b-3p and up-regulating ARHGEF9 expression
  9. L-theanine induces skeletal muscle fiber type transformation by activation of prox1/CaN signaling pathway in C2C12 myotubes
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https://doi.org/10.1515/hsz-2022-0153
Keywords for this article
apoptosis; ARHGEF9; gastric cancer; lncRNA-p21; miR-514b-3p

Articles in the same Issue

  1. Frontmatter
  2. Research Articles/Short Communications
  3. Cell Biology and Signaling
  4. Diselenide-derivative of 3-pyridinol targets redox enzymes leading to cell cycle deregulation and apoptosis in A549 cells
  5. NF90/NFAR (nuclear factors associated with dsRNA) – a new methylation substrate of the PRMT5-WD45-RioK1 complex
  6. PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1
  7. Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways
  8. LncRNA-p21 suppresses cell proliferation and induces apoptosis in gastric cancer by sponging miR-514b-3p and up-regulating ARHGEF9 expression
  9. L-theanine induces skeletal muscle fiber type transformation by activation of prox1/CaN signaling pathway in C2C12 myotubes
  10. Proteolysis
  11. TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region
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