Startseite Lebenswissenschaften LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147

Dieser Artikel wurde zurückgezogen. Rücknahme-Notiz.
  • Dejun Xu , Tianji Liu , Liu He , Dongmei Han , Ying Ma und Jianshi Du ORCID logo EMAIL logo
Veröffentlicht/Copyright: 31. Januar 2020
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 401 Heft 5

Abstract

Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been identified as a regulatory molecule in angiogenesis. The goal of this study was to illustrate how MEG3 affects the angiogenesis of vascular endothelial cells. Expression of MEG3, miR-147 and intracellular cell adhesion molecule-1 (ICAM-1) in human microvascular endothelial cell line (HMEC-1) was altered by transfection, then cell viability, apoptosis, migration, tube formation, as well as the correlation among MEG3, miR-147 and ICAM-1 were explored. MEG3 was down-regulated during tube formation of HMEC-1 cells. MEG3 expression suppressed cells viability, migration and tube formation, while it induced apoptosis. MEG3 could bind with miR-147 and repress miR-147 expression. MiR-147 induced ICAM-1 expression, and contained ICAM-1 target sequences. The anti-atherogenic actions of MEG3 were inhibited by miR-147, and the anti-atherogenic actions of miR-147 suppression were also inhibited when ICAM-1 was overexpressed. Further, ICAM-1 overexpression showed activated roles in Wnt/β-catenin and Jak/Stat signaling pathways. In low-density lipoprotein receptor (Ldlr)−/− mice, MEG3 overexpression reduced CD68+, CD3+ and ICAM-1 areas in lesions and increased collagen content. MEG3 inhibited HMEC-1 cell growth, migration and tube formation. The anti-atherogenic actions of MEG3 might be mediated via sponging miR-147, and thereby repressing the expression of ICAM-1.

Keywords: atherosclerosis; HMEC-1 cells; ICAM-1; MEG3; miR-147; tube formation

  1. Conflict of interest statement: The authors declare that they have no conflict of interest regarding this study.

References

Balik, V., Srovnal, J., Sulla, I., Kalita, O., Foltanova, T., Vaverka, M., Hrabalek, L., and Hajduch, M. (2013). MEG3: a novel long noncoding potentially tumour-suppressing RNA in meningiomas. J. Neurooncol. 112, 1–8.10.1007/s11060-012-1038-6Suche in Google Scholar

Binse, I., Ueberberg, B., Sandalcioglu, I.E., Flitsch, J., Luedecke, D.K., Mann, K., and Petersenn, S. (2014). Expression analysis of GADD45gamma, MEG3, and p8 in pituitary adenomas. Horm. Metab. Res. 46, 644–650.10.1055/s-0034-1383566Suche in Google Scholar

Braun, M., Pietsch, P., Schror, K., Baumann, G., and Felix, S.B. (1999). Cellular adhesion molecules on vascular smooth muscle cells. Cardiovasc. Res. 41, 395–401.10.1016/S0008-6363(98)00302-2Suche in Google Scholar

Cao, M.X., Jiang, Y.P., Tang, Y.L., and Liang, X.H. (2017). The crosstalk between lncRNA and microRNA in cancer metastasis: orchestrating the epithelial-mesenchymal plasticity. Oncotarget 8, 12472–12483.10.18632/oncotarget.13957Suche in Google Scholar PubMed PubMed Central

Chunharojrith, P., Nakayama, Y., Jiang, X., Kery, R.E., Ma, J., De La Hoz Ulloa, C.S., Zhang, X., Zhou, Y., and Klibanski, A. (2015). Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line. Mol. Cell. Endocrinol. 416, 27–35.10.1016/j.mce.2015.08.018Suche in Google Scholar PubMed PubMed Central

Congrains, A., Kamide, K., Oguro, R., Yasuda, O., Miyata, K., Yamamoto, E., Kawai, T., Kusunoki, H., Yamamoto, H., Takeya, Y., et al. (2012). Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B. Atherosclerosis 220, 449–455.10.1016/j.atherosclerosis.2011.11.017Suche in Google Scholar PubMed

Duzagac, F., Inan, S., Ela Simsek, F., Acikgoz, E., Guven, U., Khan, S.A., Rouhrazi, H., Oltulu, F., Aktug, H., Erol, A., et al. (2015). JAK/STAT pathway interacts with intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) while prostate cancer stem cells form tumor spheroids. J. Buon. 20, 1250–1257.Suche in Google Scholar

Fabian, M.R., Sonenberg, N., and Filipowicz, W. (2010). Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem. 79, 351–379.10.1146/annurev-biochem-060308-103103Suche in Google Scholar PubMed

Ferrara, N. (2009). Vascular endothelial growth factor. Arterioscler Thromb. Vasc. Biol. 29, 789–791.10.1161/ATVBAHA.108.179663Suche in Google Scholar PubMed

Greife, A., Knievel, J., Ribarska, T., Niegisch, G., and Schulz, W.A. (2014). Concomitant downregulation of the imprinted genes DLK1 and MEG3 at 14q32.2 by epigenetic mechanisms in urothelial carcinoma. Clin. Epigenetics 6, 29.10.1186/1868-7083-6-29Suche in Google Scholar PubMed PubMed Central

Grote, K., Luchtefeld, M., and Schieffer, B. (2005). JANUS under stress–role of JAK/STAT signaling pathway in vascular diseases. Vascul. Pharmacol. 43, 357–363.10.1016/j.vph.2005.08.021Suche in Google Scholar PubMed

Han, L., Dong, Z., Liu, N., Xie, F., and Wang, N. (2017). Maternally expressed gene 3 (MEG3) enhances PC12 cell hypoxia injury by targeting MiR-147. Cell. Physiol. Biochem. 43, 2457–2469.10.1159/000484452Suche in Google Scholar

He, Y., Luo, Y., Liang, B., Ye, L., Lu, G., and He, W. (2017a). Potential applications of MEG3 in cancer diagnosis and prognosis. Oncotarget 8, 73282–73295.10.18632/oncotarget.19931Suche in Google Scholar

He, C., Yang, W., Yang, J., Ding, J., Li, S., Wu, H., Zhou, F., Jiang, Y., Teng, L., and Yang, J. (2017b). Long noncoding RNA MEG3 negatively regulates proliferation and angiogenesis in vascular endothelial cells. DNA Cell Biol. 36, 475–481.10.1089/dna.2017.3682Suche in Google Scholar

Holdt, L.M., Beutner, F., Scholz, M., Gielen, S., Gabel, G., Bergert, H., Schuler, G., Thiery, J., and Teupser, D. (2010). ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler. Thromb. Vasc. Biol. 30, 620–627.10.1161/ATVBAHA.109.196832Suche in Google Scholar

Jalali, S., Bhartiya, D., Lalwani, M.K., Sivasubbu, S., and Scaria, V. (2013). Systematic transcriptome wide analysis of lncRNA-miRNA interactions. PLoS One 8, e53823.10.1371/journal.pone.0053823Suche in Google Scholar

Janowski, B.A., Younger, S.T., Hardy, D.B., Ram, R., Huffman, K.E., and Corey, D.R. (2007). Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat. Chem. Biol. 3, 166–173.10.1038/nchembio860Suche in Google Scholar

Li, Z.Y., Yang, L., Liu, X.J., Wang, X.Z., Pan, Y.X., and Luo, J.M. (2018a). Corrigendum to “the long noncoding RNA MEG3 and its target miR-147 regulate JAK/STAT pathway in advanced chronic myeloid leukemia” [EBioMedicine 35 (2018) 61–75]. EBioMedicine 37, 569.10.1016/j.ebiom.2018.10.049Suche in Google Scholar

Li, Z.Y., Yang, L., Liu, X.J., Wang, X.Z., Pan, Y.X., and Luo, J.M. (2018b). The long noncoding RNA MEG3 and its target miR-147 regulate JAK/STAT pathway in advanced chronic myeloid leukemia. EBioMedicine 34, 61–75.10.1016/j.ebiom.2018.07.013Suche in Google Scholar

Liu, Y., Zheng, L., Wang, Q., and Hu, Y.W. (2017). Emerging roles and mechanisms of long noncoding RNAs in atherosclerosis. Int. J. Cardiol. 228, 570–582.10.1016/j.ijcard.2016.11.182Suche in Google Scholar

Lopez, A.D., Mathers, C.D., Ezzati, M., Jamison, D.T., and Murray, C.J. (2006). Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367, 1747–1757.10.1016/S0140-6736(06)68770-9Suche in Google Scholar

Mattick, J.S. and Makunin, I.V. (2006). Non-coding RNA. Hum. Mol. Genet. 15 (Spec No 1), R17–R29.10.1093/hmg/ddl046Suche in Google Scholar PubMed

Mendes, D.S., Dantas, M.L., Gomes, J.M., Santos, W.L., Silva, A.Q., Guimaraes, L.H., Machado, P.R., Carvalho, E.M., and Arruda, S. (2013). Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis. Mem. Inst. Oswaldo Cruz. 108, 18–22.10.1590/S0074-02762013000100003Suche in Google Scholar PubMed PubMed Central

Miyoshi, N., Wagatsuma, H., Wakana, S., Shiroishi, T., Nomura, M., Aisaka, K., Kohda, T., Surani, M.A., Kaneko-Ishino, T., and Ishino, F. (2000). Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells 5, 211–220.10.1046/j.1365-2443.2000.00320.xSuche in Google Scholar PubMed

Ortiz-Munoz, G., Martin-Ventura, J.L., Hernandez-Vargas, P., Mallavia, B., Lopez-Parra, V., Lopez-Franco, O., Munoz-Garcia, B., Fernandez-Vizarra, P., Ortega, L., Egido, J., et al. (2009). Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses during atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29, 525–531.10.1161/ATVBAHA.108.173781Suche in Google Scholar PubMed

Pan, J.X. (2017). LncRNA H19 promotes atherosclerosis by regulating MAPK and NF-κB signaling pathway. Eur. Rev. Med. Pharmacol. Sci. 21, 322–328.Suche in Google Scholar

Parma, L., Baganha, F., Quax, P.H.A., and de Vries, M.R. (2017). Plaque angiogenesis and intraplaque hemorrhage in atherosclerosis. Eur. J. Pharmacol. 816, 107–115.10.1016/j.ejphar.2017.04.028Suche in Google Scholar PubMed

Place, R.F., Li, L.C., Pookot, D., Noonan, E.J., and Dahiya, R. (2008). MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc. Natl. Acad. Sci. USA 105, 1608–1613.10.1073/pnas.0707594105Suche in Google Scholar PubMed PubMed Central

Qiu, G.Z., Tian, W., Fu, H.T., Li, C.P., and Liu, B. (2016). Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction. Biochem. Biophys. Res. Commun. 471, 135–141.10.1016/j.bbrc.2016.01.164Suche in Google Scholar PubMed

Rane, S.G. and Reddy, E.P. (2002). JAKs, STATs and Src kinases in hematopoiesis. Oncogene 21, 3334–3358.10.1038/sj.onc.1205398Suche in Google Scholar PubMed

Reis, M. and Liebner, S. (2013). Wnt signaling in the vasculature. Exp. Cell Res. 319, 1317–1323.10.1016/j.yexcr.2012.12.023Suche in Google Scholar PubMed

Shibuya, M. and Claesson-Welsh, L. (2006). Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp. Cell Res. 312, 549–560.10.1016/j.yexcr.2005.11.012Suche in Google Scholar PubMed

Su, W., Xie, W., Shang, Q., and Su, B. (2015). The long noncoding RNA MEG3 is downregulated and inversely associated with VEGF levels in osteoarthritis. Biomed. Res. Int. 2015, 356893.10.1155/2015/356893Suche in Google Scholar PubMed PubMed Central

Vallee, A., Vallee, J.N., and Lecarpentier, Y. (2019). Metabolic reprogramming in atherosclerosis: opposed interplay between the canonical WNT/β-catenin pathway and PPARgamma. J. Mol. Cell. Cardiol. 133, 36–46.10.1016/j.yjmcc.2019.05.024Suche in Google Scholar PubMed

Wang, X., Wang, Z., Wang, J., Wang, Y., Liu, L., and Xu, X. (2017). LncRNA MEG3 has anti-activity effects of cervical cancer. Biomed. Pharmacother. 94, 636–643.10.1016/j.biopha.2017.07.056Suche in Google Scholar PubMed

Weber, C. and Noels, H. (2011). Atherosclerosis: current pathogenesis and therapeutic options. Nat. Med. 17, 1410–1422.10.1038/nm.2538Suche in Google Scholar PubMed

Wong, D.W.L., Yiu, W.H., Chan, K.W., Li, Y., Li, B., Lok, S.W.Y., Taketo, M.M., Igarashi, P., Chan, L.Y.Y., Leung, J.C.K., et al. (2018). Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria. Kidney Int. 93, 1367–1383.10.1016/j.kint.2017.12.017Suche in Google Scholar PubMed PubMed Central

Wright, M., Aikawa, M., Szeto, W., and Papkoff, J. (1999). Identification of a Wnt-responsive signal transduction pathway in primary endothelial cells. Biochem. Biophys. Res. Commun. 263, 384–388.10.1006/bbrc.1999.1344Suche in Google Scholar PubMed

Wu, Z., He, Y., Li, D., Fang, X., Shang, T., Zhang, H., and Zheng, X. (2017). Long noncoding RNA MEG3 suppressed endothelial cell proliferation and migration through regulating miR-21. Am. J. Transl. Res. 9, 3326–3335.Suche in Google Scholar

Zhang, Y., Liu, X., Bai, X., Lin, Y., Li, Z., Fu, J., Li, M., Zhao, T., Yang, H., Xu, R., et al. (2017a). Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR-223/NLRP3 axis. J. Pineal Res. 64, e12449.10.1111/jpi.12449Suche in Google Scholar PubMed

Zhang, J., Yao, T., Lin, Z., and Gao, Y. (2017b). Aberrant methylation of MEG3 functions as a potential plasma-based biomarker for cervical cancer. Sci. Rep. 7, 6271.10.1038/s41598-017-06502-7Suche in Google Scholar PubMed PubMed Central

Zhou, Y., Zhang, X., and Klibanski, A. (2012). MEG3 noncoding RNA: a tumor suppressor. J. Mol. Endocrinol. 48, R45–R53.10.1530/JME-12-0008Suche in Google Scholar PubMed PubMed Central

Received: 2019-04-18
Accepted: 2019-12-17
Published Online: 2020-01-31
Published in Print: 2020-04-28

©2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Power to the daughters – mitochondrial and mtDNA transmission during cell division
  4. Dr. NO and Mr. Toxic – the versatile role of nitric oxide
  5. Diffuse or hitch a ride: how photoreceptor lipidated proteins get from here to there
  6. Human papillomavirus oncoproteins and post-translational modifications: generating multifunctional hubs for overriding cellular homeostasis
  7. Research Articles/Short Communications
  8. Genes and Nucleic Acids
  9. LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147
  10. Membranes, Lipids, Glycobiology
  11. The redox status of cysteine thiol residues of apolipoprotein E impacts on its lipid interactions
  12. Proteolysis
  13. Characterization of substrate specificity and novel autoprocessing mechanism of dipeptidase A from Prevotella intermedia
https://doi.org/10.1515/hsz-2019-0230
Schlagwörter für diesen Artikel
atherosclerosis; HMEC-1 cells; ICAM-1; MEG3; miR-147; tube formation

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Power to the daughters – mitochondrial and mtDNA transmission during cell division
  4. Dr. NO and Mr. Toxic – the versatile role of nitric oxide
  5. Diffuse or hitch a ride: how photoreceptor lipidated proteins get from here to there
  6. Human papillomavirus oncoproteins and post-translational modifications: generating multifunctional hubs for overriding cellular homeostasis
  7. Research Articles/Short Communications
  8. Genes and Nucleic Acids
  9. LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147
  10. Membranes, Lipids, Glycobiology
  11. The redox status of cysteine thiol residues of apolipoprotein E impacts on its lipid interactions
  12. Proteolysis
  13. Characterization of substrate specificity and novel autoprocessing mechanism of dipeptidase A from Prevotella intermedia
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 29.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2019-0230/html
Button zum nach oben scrollen