MiR-188-3p and MiR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma Via Post-Transcriptional Suppression of NDRG1

Overview

Journal Technol Cancer Res Treat

Specialties Biomedical Engineering
Oncology
Pharmacology

Date 2021 Aug 6

PMID 34355586

Citations 9

Authors

Zhenzhao Luo

Yue Fan

Xianchang Liu

Shuiyi Liu

Xiaoyu Kong

Zhonghuan Ding

Ying Li

Liqing Wei

Affiliations

Soon will be listed here.

Abstract

Background: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown.

Methods: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells.

Results: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3'UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration.

Conclusions: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.

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References

Yan X, Chua M, Sun H, So S . N-Myc down-regulated gene 1 mediates proliferation, invasion, and apoptosis of hepatocellular carcinoma cells. Cancer Lett. 2008; 262(1):133-42. DOI: 10.1016/j.canlet.2007.12.010. View

Pan J, Sun C, Bi Z, Chen Z, Li S, Li Q . miR-206/133b Cluster: A Weapon against Lung Cancer?. Mol Ther Nucleic Acids. 2017; 8:442-449. PMC: 5542379. DOI: 10.1016/j.omtn.2017.06.002. View

Xu X, Liu Z, Wang J, Xie H, Li J, Cao J . Global proteomic profiling in multistep hepatocarcinogenesis and identification of PARP1 as a novel molecular marker in hepatocellular carcinoma. Oncotarget. 2016; 7(12):13730-41. PMC: 4924674. DOI: 10.18632/oncotarget.7316. View

Azuma K, Kawahara A, Hattori S, Taira T, Tsurutani J, Watari K . NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer. J Thorac Oncol. 2012; 7(5):779-89. DOI: 10.1097/JTO.0b013e31824c92b4. View

Jiang F, Yu Q, Chu Y, Zhu X, Lu W, Liu Q . MicroRNA-98-5p inhibits proliferation and metastasis in non-small cell lung cancer by targeting TGFBR1. Int J Oncol. 2018; 54(1):128-138. PMC: 6255066. DOI: 10.3892/ijo.2018.4610. View

Mao Z, Sun J, Feng B, Ma J, Zang L, Dong F . The metastasis suppressor, N-myc downregulated gene 1 (NDRG1), is a prognostic biomarker for human colorectal cancer. PLoS One. 2013; 8(7):e68206. PMC: 3706595. DOI: 10.1371/journal.pone.0068206. View

Dickinson A, Saraswat M, Makitie A, Silen R, Hagstrom J, Haglund C . Label-free tissue proteomics can classify oral squamous cell carcinoma from healthy tissue in a stage-specific manner. Oral Oncol. 2018; 86:206-215. DOI: 10.1016/j.oraloncology.2018.09.013. View

Nishio S, Ushijima K, Tsuda N, Takemoto S, Kawano K, Yamaguchi T . Cap43/NDRG1/Drg-1 is a molecular target for angiogenesis and a prognostic indicator in cervical adenocarcinoma. Cancer Lett. 2008; 264(1):36-43. DOI: 10.1016/j.canlet.2008.01.020. View

Hayes C, Chayama K . MicroRNAs as Biomarkers for Liver Disease and Hepatocellular Carcinoma. Int J Mol Sci. 2016; 17(3):280. PMC: 4813144. DOI: 10.3390/ijms17030280. View

10.

Fang B, Kovacevic Z, Park K, Kalinowski D, Jansson P, Lane D . Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy. Biochim Biophys Acta. 2013; 1845(1):1-19. DOI: 10.1016/j.bbcan.2013.11.002. View

11.

Pradhan A, Emdad L, Das S, Sarkar D, Fisher P . The Enigma of miRNA Regulation in Cancer. Adv Cancer Res. 2017; 135:25-52. DOI: 10.1016/bs.acr.2017.06.001. View

12.

Servin-Gonzalez L, Granados-Lopez A, Lopez J . Families of microRNAs Expressed in Clusters Regulate Cell Signaling in Cervical Cancer. Int J Mol Sci. 2015; 16(6):12773-90. PMC: 4490472. DOI: 10.3390/ijms160612773. View

13.

Ma J, Gao Q, Zeng S, Shen H . Knockdown of NDRG1 promote epithelial-mesenchymal transition of colorectal cancer via NF-κB signaling. J Surg Oncol. 2016; 114(4):520-7. DOI: 10.1002/jso.24348. View

14.

Peng Y, Shen X, Jiang H, Chen Z, Wu J, Zhu Y . miR-188-5p Suppresses Gastric Cancer Cell Proliferation and Invasion via Targeting ZFP91. Oncol Res. 2018; 27(1):65-71. PMC: 7848256. DOI: 10.3727/096504018X15191223015016. View

15.

Kawahara A, Akiba J, Hattori S, Yamaguchi T, Abe H, Taira T . Nuclear expression of N-myc downstream regulated gene 1/Ca(2+)-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer. Exp Ther Med. 2012; 2(3):471-479. PMC: 3440729. DOI: 10.3892/etm.2011.222. View

16.

Chang X, Xu X, Ma J, Xue X, Li Z, Deng P . NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells. Mol Biol Rep. 2014; 41(9):6215-23. DOI: 10.1007/s11033-014-3501-2. View

17.

Oukka M, Wein M, Glimcher L . Schnurri-3 (KRC) interacts with c-Jun to regulate the IL-2 gene in T cells. J Exp Med. 2004; 199(1):15-24. PMC: 1887724. DOI: 10.1084/jem.20030421. View

18.

Wang Y, Zhou Y, Tao F, Chai S, Xu X, Yang Y . N-myc downstream regulated gene 1(NDRG1) promotes the stem-like properties of lung cancer cells through stabilized c-Myc. Cancer Lett. 2017; 401:53-62. DOI: 10.1016/j.canlet.2017.04.031. View

19.

Dai J, Wu H, Zhang Y, Gao K, Hu G, Guo Y . Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression. Oncotarget. 2016; 7(52):87147-87160. PMC: 5349978. DOI: 10.18632/oncotarget.13515. View

20.

Cheng J, Xie H, Xu X, Wu J, Wei X, Su R . NDRG1 as a biomarker for metastasis, recurrence and of poor prognosis in hepatocellular carcinoma. Cancer Lett. 2011; 310(1):35-45. DOI: 10.1016/j.canlet.2011.06.001. View