MiR‑29a‑3p Represses Proliferation and Metastasis of Gastric Cancer Cells Via Attenuating HAS3 Levels

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2018 Apr 26

PMID 29693123

Citations 15

Authors

Feihu Bai

Mengna Jiu

Yanjie You

Yaning Feng

Ruijuan Xin

Xiaogang Liu

Lirong Mo

Yongzhan Nie

Affiliations

Soon will be listed here.

Abstract

MicroRNA‑29a (miR‑29a) has recently been in the spotlight as a tumor suppressor whose encoding gene is frequently suppressed in cancers. The aim of the present study was to investigate the biological functions and underlying molecular mechanism by which miR‑29a‑3p suppresses gastric cancer peritoneum metastasis. Cell proliferation, colony‑forming, wound healing and Transwell migration assays were performed in the present study. MiR‑29a‑3p expression was markedly decreased in gastric cancer cell lines with stronger metastatic potential. Silencing miR‑29a‑3p expression promoted gastric cancer cell proliferation, colony‑forming, migration and invasion. By contrast, overexpression of miR‑29a‑3p inhibited these biological phenotypes. In addition, it was revealed that miR‑29a‑3p functioned through downregulating hyaluronan synthase 3 expression. Collectively, dysregulated miR‑29a‑3p expression in gastric cancer cells was associated with malignant properties primarily relevant to migration and metastasis. The results suggest that miR‑29a‑3p may be a potential therapeutic target for gastric cancer.

Citing Articles

Long non-coding RNA CRNDE promotes the progress of hypertrophic scar via regulating the proliferation and migration of hypertrophic scar fibroblasts through targeting microRNA-29a-3p.

Wang Z, Wu X, Zeng L Arch Dermatol Res. 2025; 317(1):440.

PMID: 39976754 DOI: 10.1007/s00403-025-03939-z.

Prediction of novel biomarkers for gastric intestinal metaplasia and gastric adenocarcinoma using bioinformatics analysis.

Eskandarion M, Eskandarieh S, Shakoori Farahani A, Mahmoodzadeh H, Shahi F, Oghabian M Heliyon. 2024; 10(9):e30253.

PMID: 38737262 PMC: 11088262. DOI: 10.1016/j.heliyon.2024.e30253.

Bioinformatics and pathway enrichment analysis identified hub genes and potential biomarker for gastric cancer prognosis.

Darang E, Pezeshkian Z, Mirhoseini S, Ghovvati S Front Oncol. 2023; 13:1187521.

PMID: 37361568 PMC: 10288990. DOI: 10.3389/fonc.2023.1187521.

Role of exosomal ncRNAs released by M2 macrophages in tumor progression of gastrointestinal cancers.

Meyiah A, Alahdal M, Elkord E iScience. 2023; 26(4):106333.

PMID: 36968082 PMC: 10031147. DOI: 10.1016/j.isci.2023.106333.

Role of PAX2 in breast cancer verified by bioinformatics analysis and validation.

Yang S, Gao W, Wang H, Zhang X, Mi Y, Ding Y Ann Transl Med. 2023; 11(2):58.

PMID: 36819548 PMC: 9929765. DOI: 10.21037/atm-22-6360.

References

Rigoutsos I . New tricks for animal microRNAS: targeting of amino acid coding regions at conserved and nonconserved sites. Cancer Res. 2009; 69(8):3245-8. DOI: 10.1158/0008-5472.CAN-09-0352. View

Mizuno K, Seki N, Mataki H, Matsushita R, Kamikawaji K, Kumamoto T . Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma. Int J Oncol. 2015; 48(2):450-60. PMC: 4725458. DOI: 10.3892/ijo.2015.3289. View

Yang L . Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006; 12(1):17-20. PMC: 4077485. DOI: 10.3748/wjg.v12.i1.17. View

Kuo Y, Fang W, Huang C, Tsai S, Wang Y, Yang C . Hyaluronan synthase 3 mediated oncogenic action through forming inter-regulation loop with tumor necrosis factor alpha in oral cancer. Oncotarget. 2017; 8(9):15563-15583. PMC: 5362506. DOI: 10.18632/oncotarget.14697. View

Jiang H, Zhang G, Wu J, Jiang C . Diverse roles of miR-29 in cancer (review). Oncol Rep. 2014; 31(4):1509-16. DOI: 10.3892/or.2014.3036. View

Auvinen P, Rilla K, Tumelius R, Tammi M, Sironen R, Soini Y . Hyaluronan synthases (HAS1-3) in stromal and malignant cells correlate with breast cancer grade and predict patient survival. Breast Cancer Res Treat. 2013; 143(2):277-86. DOI: 10.1007/s10549-013-2804-7. View

Zhou Q, Costinean S, Croce C, Brasier A, Merwat S, Larson S . MicroRNA 29 targets nuclear factor-κB-repressing factor and Claudin 1 to increase intestinal permeability. Gastroenterology. 2014; 148(1):158-169.e8. PMC: 4303568. DOI: 10.1053/j.gastro.2014.09.037. View

Xu X, Wu X, Fan Y, Tan B, Quan Z, Luo C . Exosome-derived microRNA-29c induces apoptosis of BIU-87 cells by down regulating BCL-2 and MCL-1. Asian Pac J Cancer Prev. 2014; 15(8):3471-6. DOI: 10.7314/apjcp.2014.15.8.3471. View

Lin C, Xin S, Qin X, Li H, Lin L, You Y . Zoledronic acid suppresses metastasis of esophageal squamous cell carcinoma cells through upregulating the tight junction protein occludin. Cytotechnology. 2015; 68(4):1233-41. PMC: 4960172. DOI: 10.1007/s10616-015-9884-7. View

10.

Bullard K, Kim H, Wheeler M, Wilson C, Neudauer C, Simpson M . Hyaluronan synthase-3 is upregulated in metastatic colon carcinoma cells and manipulation of expression alters matrix retention and cellular growth. Int J Cancer. 2003; 107(5):739-46. DOI: 10.1002/ijc.11475. View

11.

Oliveira L, Schiavinato J, Fraguas M, Lucena-Araujo A, Haddad R, Araujo A . Potential roles of microRNA-29a in the molecular pathophysiology of T-cell acute lymphoblastic leukemia. Cancer Sci. 2015; 106(10):1264-77. PMC: 4637998. DOI: 10.1111/cas.12766. View

12.

Nishikawa R, Chiyomaru T, Enokida H, Inoguchi S, Ishihara T, Matsushita R . Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma. FEBS Lett. 2015; 589(16):2136-45. DOI: 10.1016/j.febslet.2015.06.005. View

13.

Bae H, Noh J, Kim J, Eun J, Jung K, Kim M . MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene. 2013; 33(20):2557-67. DOI: 10.1038/onc.2013.216. View

14.

Zhao S, Yao D, Chen J, Ding N . Aberrant expression of miR-20a and miR-203 in cervical cancer. Asian Pac J Cancer Prev. 2013; 14(4):2289-93. DOI: 10.7314/apjcp.2013.14.4.2289. View

15.

Xiong Y, Fang J, Yun J, Yang J, Zhang Y, Jia W . Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 2009; 51(3):836-45. DOI: 10.1002/hep.23380. View

16.

Yu P, Yan M, Lai H, Huang R, Chou Y, Lin W . Downregulation of miR-29 contributes to cisplatin resistance of ovarian cancer cells. Int J Cancer. 2013; 134(3):542-51. DOI: 10.1002/ijc.28399. View

17.

Crew K, Neugut A . Epidemiology of gastric cancer. World J Gastroenterol. 2006; 12(3):354-62. PMC: 4066052. DOI: 10.3748/wjg.v12.i3.354. View

18.

He H, Di Y, Liang M, Yang F, Yao L, Hao S . The microRNA-218 and ROBO-1 signaling axis correlates with the lymphatic metastasis of pancreatic cancer. Oncol Rep. 2013; 30(2):651-8. DOI: 10.3892/or.2013.2516. View

19.

Xu Y, Wu H, Ma H, Xu L, Huo Y, Yin L . MicroRNA-503 suppresses proliferation and cell-cycle progression of endometrioid endometrial cancer by negatively regulating cyclin D1. FEBS J. 2013; 280(16):3768-79. DOI: 10.1111/febs.12365. View

20.

Takabe P, Bart G, Ropponen A, Rilla K, Tammi M, Tammi R . Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion. Exp Cell Res. 2015; 337(1):1-15. DOI: 10.1016/j.yexcr.2015.07.026. View