MicroRNA-627-5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator.

Publisher: Wiley-Blackwell Country of Publication: Australia NLM ID: 0425076 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1681 (Electronic) Linking ISSN: 03051870 NLM ISO Abbreviation: Clin Exp Pharmacol Physiol Subsets: MEDLINE

Publication: Oxford, England : Wiley-Blackwell
Original Publication: Oxford, Blackwell Scientific Publications.

B-Cell Lymphoma 3 Protein/*biosynthesis ; Carcinoma, Hepatocellular/*metabolism ; Cell Proliferation/*physiology ; Liver Neoplasms/*metabolism ; MicroRNAs/*biosynthesis; Animals ; B-Cell Lymphoma 3 Protein/antagonists & inhibitors ; Carcinoma, Hepatocellular/pathology ; Hep G2 Cells ; Humans ; Liver Neoplasms/pathology ; Mice ; Xenograft Model Antitumor Assays/methods

Hepatocellular carcinoma (HCC) is a common malignant tumour. An increasing number of studies indicate that microRNAs (miRNAs) are critical regulators in the carcinogenesis and progression of HCC. MiR-627-5p has been identified as a tumour suppressor in colorectal cancer and glioblastoma multiforme. However, the function of miR-627-5p in HCC progression remains unclear yet. In our present study, miR-627-5p was determined to be low-expressed in HCC tissues and cell lines. Furthermore, miR-627-5p was expressed at significantly lower levels in HCC tissues with tumour size >5 cm or advanced tumour stages (III+IV). Additionally, HCC patients with low miR-627-5p level had a significantly poorer overall survival. Functionally, ectopic expression of miR-627-5p obviously inhibited the proliferation, and induced G1 phase arrest and apoptosis of Hep3B and SMMC-7721 cells. Conversely, miR-627-5p silencing facilitated HCC cell proliferation, cell cycle progression and apoptosis resistance. In vivo experiments further confirmed that miR-627-5p overexpression repressed the growth of Hep3B cells in mice. Mechanistically, BCL3 transcription coactivator was predicted as a direct target of miR-627-5p. MiR-627-5p overexpression reduced, whereas miR-627-5p knockdown enhanced the expression of BCL3 protein in HCC cells. Luciferase reporter assay confirmed the direct binding between miR-627-5p and 3'UTR of BCL3. The expression of BCL3 protein was negatively correlated with miR-627-5p level in HCC tissues. More importantly, re-expression of BCL3 partially reversed miR-627-5p induced inhibitory effects on Hep3B cells. In conclusion, these results demonstrated that miR-627-5p functioned as a tumour suppressor in HCC possibly by attenuating BCL3. This finding might offer a new therapeutic target for HCC treatment.
(© 2019 John Wiley & Sons Australia, Ltd.)

Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115-132.
Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380(15):1450-1462.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-297.
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857-866.
Croce CM, Calin GA. miRNAs, cancer, and stem cell division. Cell. 2005;122(1):6-7.
Garzon R, Calin GA, Croce CM. MicroRNAs in Cancer. Annu Rev Med. 2009;60:167-179.
Xu Q, Zhu Q, Zhou Z, et al. MicroRNA-876-5p inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by targeting BCL6 corepressor like 1. Biomed Pharmacother. 2018;103:645-652.
Xu Q, Liu X, Liu Z, et al. MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway. Mol Cancer. 2017;16(1):103.
Wang Y, Yang L, Chen T, et al. A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis. Mol Cancer. 2019;18(1):28.
Zhang L, Wang L, Wang Y, et al. LncRNA KTN1-AS1 promotes tumor growth of hepatocellular carcinoma by targeting miR-23c/ERBB2IP axis. Biomed Pharmacother. 2019;109:1140-1147.
Liu Z, Wang Y, Dou C, et al. Hypoxia-induced up-regulation of VASP promotes invasiveness and metastasis of hepatocellular carcinoma. Theranostics. 2018;8(17):4649-4663.
Dou C, Zhou Z, Xu Q, et al. Hypoxia-induced TUFT1 promotes the growth and metastasis of hepatocellular carcinoma by activating the Ca(2+)/PI3K/AKT pathway. Oncogene. 2019;38(8):1239-1255.
Liu Z, Wang Y, Dou C, et al. MicroRNA-1468 promotes tumor progression by activating PPAR-gamma-mediated AKT signaling in human hepatocellular carcinoma. J Exp Clin Cancer Res. 2018;37(1):49.
Wang Y, Liu Z, Yao B, et al. Long non-coding RNA CASC2 suppresses epithelial-mesenchymal transition of hepatocellular carcinoma cells through CASC2/miR-367/FBXW7 axis. Mol Cancer. 2017;16(1):123.
Dou C, Liu Z, Xu M, et al. miR-187-3p inhibits the metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting S100A4. Cancer Lett. 2016;381(2):380-390.
Padi SK, Zhang Q, Rustum YM, Morrison C, Guo B. MicroRNA-627 mediates the epigenetic mechanisms of vitamin D to suppress proliferation of human colorectal cancer cells and growth of xenograft tumors in mice. Gastroenterology. 2013;145(2):437-446.
Sun M, Zhang Q, Yang X, Qian SY, Guo B. Vitamin D enhances the efficacy of irinotecan through miR-627-mediated inhibition of intratumoral drug metabolism. Mol Cancer Ther. 2016;15(9):2086-2095.
Li Z, Zhang J, Zheng H, et al. Modulating lncRNA SNHG15/CDK6/miR-627 circuit by palbociclib, overcomes temozolomide resistance and reduces M2-polarization of glioma associated microglia in glioblastoma multiforme. J Exp Clin Cancer Res. 2019;38(1):380.
Shin VY, Ng EK, Chan VW, Kwong A, Chu KM. A three-miRNA signature as promising non-invasive diagnostic marker for gastric cancer. Mol Cancer. 2015;14:202.
Yang JH, Li JH, Shao P, Zhou H, Chen YQ, Qu LH. starBase: a database for exploring microRNA-mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data. Nucleic Acids Res. 2011;39(Database issue):D202-D209.
Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42(Database issue):D92-D97.
Tu K, Liu Z, Yao B, et al. BCL-3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1. Oncol Rep. 2016;35(4):2382-2390.
Xie KL, Zhang YG, Liu J, Zeng Y, Wu H. MicroRNAs associated with HBV infection and HBV-related HCC. Theranostics. 2014;4(12):1176-1192.
Li X, Yang W, Lou L, Chen Y, Wu S, Ding G. microRNA: a promising diagnostic biomarker and therapeutic target for hepatocellular carcinoma. Dig Dis Sci. 2014;59(6):1099-1107.
Wong CM, Tsang FH, Ng IO. Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications. Nat Rev Gastroenterol Hepatol. 2018;15(3):137-151.
Sadri Nahand J, Bokharaei-Salim F, Salmaninejad A, et al. microRNAs: key players in virus-associated hepatocellular carcinoma. J Cell Physiol. 2019;234(8):12188-12225.
Wang H, Xiong M, Hu Y, Sun Y, Ma Q. MicroRNA-19b inhibits proliferation of gastric cancer cells by targeting B-cell CLL/lymphoma 3. Oncol Rep. 2016;36(4):2079-2086.
Guan Y, Yao H, Zheng Z, Qiu G, Sun K. MiR-125b targets BCL3 and suppresses ovarian cancer proliferation. Int J Cancer. 2011;128(10):2274-2283.
Luo S, Wang J, Ma Y, Yao Z, Pan H. PPARgamma inhibits ovarian cancer cells proliferation through upregulation of miR-125b. Biochem Biophys Res Commun. 2015;462(2):85-90.
Park SG, Chung C, Kang H, Kim JY, Jung G. Up-regulation of cyclin D1 by HBx is mediated by NF-kappaB2/BCL3 complex through kappaB site of cyclin D1 promoter. J Biol Chem. 2006;281(42):31770-31777.

Keywords: BCL3; hepatocellular carcinoma; miR-627-5p; proliferation; tumour growth

0 (B-Cell Lymphoma 3 Protein)
0 (BCL3 protein, human)
0 (MIRN627 microRNA, human)
0 (MicroRNAs)

Date Created: 20191204 Date Completed: 20210507 Latest Revision: 20210507

20231215

10.1111/1440-1681.13218

31793036