MicroRNA‑29c‑3p acts as a tumor suppressor gene and inhibits tumor progression in hepatocellular carcinoma by targeting TRIM31

Lv,Tao; Jiang,Li; Kong,Lingxiang; Yang,Jiayin

doi:10.3892/or.2020.7469

MicroRNA‑29c‑3p acts as a tumor suppressor gene and inhibits tumor progression in hepatocellular carcinoma by targeting TRIM31

Authors:
- Tao Lv
- Li Jiang
- Lingxiang Kong
- Jiayin Yang
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Affiliations: Department of Hepato‑Biliary‑Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: January 17, 2020 https://doi.org/10.3892/or.2020.7469
Pages: 953-964
Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aberrant expression of microRNAs (miRNAs) has been widely reported in many malignant tumors, and dysregulated miRNAs play an important role in the malignant progression of tumors. It has been reported that miR‑29c‑3p expression is dysregulated in tumors and promotes the development of tumors, especially in hepatocellular carcinoma (HCC). However, the specific mechanism of miR‑29c‑3p in HCC is not clear. The present study demonstrated that miR‑29c‑3p was expressed at low levels in HCC patients and cell lines and that its decreased expression was closely related to poor prognosis of HCC patients. Overexpression of miR‑29c‑3p could significantly inhibit the proliferation and migration of HCC cells in vitro and suppress the HCC tumor growth in vivo. The luciferase reporter assay demonstrated that miR‑29c‑3p directly bound to tripartite motif containing 31 (TRIM31) and suppressed TRIM31 expression. Finally, upregulation of TRIM31 could partially abolish the tumor suppressing roles of miR‑29c‑3p in HCC. Overall, miR‑29c‑3p, as a tumor suppressor gene, was revealed to inhibit the malignant progression of HCC by reducing the expression of TRIM31 and may be used as a potential therapeutic target for the precise treatment of HCC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Greten TF, Wang XW and Korangy F: Current concepts of immune based treatments for patients with HCC: From basic science to novel treatment approaches. Gut. 64:842–848. 2015. View Article : Google Scholar : PubMed/NCBI
3	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
4	Li Z and Rana TM: Therapeutic targeting of microRNAs: Current status and future challenges. Nat Rev Drug Discov. 13:622–638. 2014. View Article : Google Scholar : PubMed/NCBI
5	Dragomir MP, Knutsen E and Calin GA: SnapShot: Unconventional miRNA functions. Cell. 174:1038–1038.e1. 2018. View Article : Google Scholar : PubMed/NCBI
6	Calin GA and Croce CM: MicroRNA-cancer connection: The beginning of a new tale. Cancer Res. 66:7390–7394. 2006. View Article : Google Scholar : PubMed/NCBI
7	Hayes CN and Chayama K: MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma. Int J Mol Sci. 17:2802016. View Article : Google Scholar : PubMed/NCBI
8	Du H, Xu Q, Xiao S, Wu Z, Gong J, Liu C, Ren G and Wu H: MicroRNA-424-5p acts as a potential biomarker and inhibits proliferation and invasion in hepatocellular carcinoma by targeting TRIM29. Life Sci. 224:1–11. 2019. View Article : Google Scholar : PubMed/NCBI
9	Tang H, Lv W, Sun W, Bi Q and Hao Y: miR-505 inhibits cell growth and EMT by targeting MAP3K3 through the AKT-NFκB pathway in NSCLC cells. Int J Mol Med. 43:1203–1216. 2019.PubMed/NCBI
10	Yang L, Zhang S, Guo K, Huang H, Qi S, Yao J and Zhang Z: miR-125a restrains cell migration and invasion by targeting STAT3 in gastric cancer cells. Onco Targets Ther. 12:205–215. 2018. View Article : Google Scholar : PubMed/NCBI
11	Dong XZ, Song Y, Lu YP, Hu Y, Liu P and Zhang L: Sanguinarine inhibits the proliferation of BGC-823 gastric cancer cells via regulating miR-96-5p/miR-29c-3p and the MAPK/JNK signaling pathway. J Nat Med. 73:777–788. 2019. View Article : Google Scholar : PubMed/NCBI
12	Chen G, Zhou T, Li Y, Yu Z and Sun L: p53 target miR-29c-3p suppresses colon cancer cell invasion and migration through inhibition of PHLDB2. Biochem Biophys Res Commun. 487:90–95. 2017. View Article : Google Scholar : PubMed/NCBI
13	Lu Y, Tang L, Zhang Z, Li S, Liang S, Ji L, Yang B, Liu Y and Wei W: Long noncoding RNA TUG1/miR-29c axis affects cell proliferation, invasion, and migration in human pancreatic cancer. Dis Markers. 22:68570422018.
14	Fang R, Huang Y, Xie J, Zhang J and Ji X: Downregulation of miR-29c-3p is associated with a poor prognosis in patients with laryngeal squamous cell carcinoma. Diagn Pathol. 14:1092019. View Article : Google Scholar : PubMed/NCBI
15	Wang L, Yu T, Li W, Li M, Zuo Q, Zou Q and Xiao B: The miR-29c-KIAA1199 axis regulates gastric cancer migration by binding with WBP11 and PTP4A3. Oncogene. 38:3134–3150. 2019. View Article : Google Scholar : PubMed/NCBI
16	Zhang S, Jin J, Tian X and Wu L: sa-miR-29c-3p regulates biological function of colorectal cancer by targeting SPARC. Oncotarget. 8:104508–104524. 2017.PubMed/NCBI
17	Wu H, Zhang W, Wu Z, Liu Y, Shi Y, Gong J, Shen W and Liu C: miR-29c-3p regulates DNMT3B and LATS1 methylation to inhibit tumor progression in hepatocellular carcinoma. Cell Death Dis. 18:482019. View Article : Google Scholar
18	Lopes CB, Magalhães LL, Teófilo CR, Alves APNN, Montenegro RC, Negrini M and Ribeiro-Dos-Santos Â: Differential expression of hsa-miR-221, hsa-miR-21, hsa-miR-135b, and hsa-miR-29c suggests a field effect in oral cancer. BMC Cancer. 18:7212018. View Article : Google Scholar : PubMed/NCBI
19	Li W, Yi J, Zheng X, Liu S, Fu W, Ren L, Li L, Hoon DSB, Wang J and Du G: miR-29c plays a suppressive role in breast cancer by targeting the TIMP3/STAT1/FOXO1 pathway. Clin Epigenetics. 10:642018. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Chhabra R: miRNA and methylation: A multifaceted liaison. Chembiochem. 16:195–203. 2015. View Article : Google Scholar : PubMed/NCBI
22	Rupaimoole R and Slack FJ: MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 16:203–222. 2017. View Article : Google Scholar : PubMed/NCBI
23	Wang H, Zhu Y, Zhao M, Wu C, Zhang P, Tang L, Zhang H, Chen X, Yang Y and Liu G: miRNA-29c suppresses lung cancer cell adhesion to extracellular matrix and metastasis by targeting integrin beta1 and matrix metalloproteinase2 (MMP2). PLoS One. 8:e701922013. View Article : Google Scholar : PubMed/NCBI
24	Li L, Shou H, Wang Q and Liu S: Investigation of the potential theranostic role of KDM5B/miR-29c signaling axis in paclitaxel resistant endometrial carcinoma. Gene. 694:76–82. 2019. View Article : Google Scholar : PubMed/NCBI
25	Morita S, Horii T, Kimura M, Ochiya T, Tajima S and Hatada I: miR-29 represses the activities of DNA methyltransferases and DNA demethylases. Int J Mol Sci. 14:14647–14658. 2013. View Article : Google Scholar : PubMed/NCBI
26	Liu L, Bi N, Wu L, Ding X, Men Y, Zhou W, Li L, Zhang W, Shi S, Song Y and Wang L: MicroRNA-29c functions as a tumor suppressor by targeting VEGFA in lung adenocarcinoma. Mol Cancer. 16:502017. View Article : Google Scholar : PubMed/NCBI
27	Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, et al: The tripartite motif family identifies cell compartments. EMBO J. 20:2140–2151. 2001. View Article : Google Scholar : PubMed/NCBI
28	Song H, Liu B, Huai W, Yu Z, Wang W, Zhao J, Han L, Jiang G, Zhang L, Gao C and Zhao W: The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3. Nat Commun. 7:137272016. View Article : Google Scholar : PubMed/NCBI
29	Yu C, Chen S, Guo Y and Sun C: Oncogenic TRIM31 confers gemcitabine resistance in pancreatic cancer via activating the NF-κB signaling pathway. Theranostics. 8:3224–3236. 2018. View Article : Google Scholar : PubMed/NCBI
30	Li H, Zhang Y, Hai J, Wang J, Zhao B, Du L and Geng X: Knockdown of TRIM31 suppresses proliferation and invasion of gallbladder cancer cells by down-regulating MMP2/9 through the PI3K/Akt signaling pathway. Biomed Pharmacother. 103:1272–1278. 2018. View Article : Google Scholar : PubMed/NCBI
31	Ra EA, Lee TA, Won Kim S, Park A, Choi HJ, Jang I, Kang S, Hee Cheon J, Cho JW, Eun Lee J, et al: TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells. Nat Commun. 7:117262016. View Article : Google Scholar : PubMed/NCBI
32	Scott DC, Sviderskiy VO, Monda JK, Lydeard JR, Cho SE, Harper JW and Schulman BA: Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8. Cell. 157:1671–1684. 2014. View Article : Google Scholar : PubMed/NCBI
33	Hatakeyama S: TRIM proteins and cancer. Nat Rev Cancer. 11:792–804. 2011. View Article : Google Scholar : PubMed/NCBI
34	Sato T, Takahashi H, Hatakeyama S, Iguchi A and Ariga T: The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway. Oncogene. 34:1280–1291. 2015. View Article : Google Scholar : PubMed/NCBI