miR-451: Potential role as tumor suppressor of human hepatoma cell growth and invasion

Liu,Xuemin; Zhang,Xufeng; Xiang,Junxi; Lv,Yi; Shi,Jianhua

doi:10.3892/ijo.2014.2446

miR-451: Potential role as tumor suppressor of human hepatoma cell growth and invasion

Authors:
- Xuemin Liu
- Xufeng Zhang
- Junxi Xiang
- Yi Lv
- Jianhua Shi
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Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710004, P.R. China
Published online on: May 19, 2014 https://doi.org/10.3892/ijo.2014.2446
Pages: 739-745

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Abstract

Malignant hepatoma is the leading cause of morbidity and mortality in primary liver cancer. MicroRNAs are widely accepted to act as tumor regulators to mediate tumorigenesis. Recently, miRNA-451 (miR-451) has attracted increasing attention due to its critical roles in the development of several types of cancers. Unfortunately, its function and underlying mechanism(s) of action in hepatoma remain unclear. In this study, a significant downregulation of miR-451 was observed in hepatoma cell lines. Its overexpression by administration of miR-451 mimics decreased cell viability and promoted cell apoptosis, indicating a critical role of miR-451 in cell growth. Further mechanistic analysis suggested that miR-451 overexpression accelerated cell death in a caspase-3-dependent manner, as pretreatment with its inhibitor z-VAD-fmk notably attenuated miR-451-induced cell apoptotic rates. Moreover, miR-451 upregulation abrogated cell invasive ability, accompanied with the decrease of matrix metalloproteinase-9 (MMP-9) expression levels, which may contribute to miR-451-triggered cell apoptosis. Taken together, these results reveal a prominent role of miR-451 as a tumor suppressor regulating hepatoma cell growth and invasion in a caspase-3- and MMP-9-dependent manner. Thus, our research supports this promising therapeutic agent against hepatoma.

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1	Yang JD and Roberts LR: Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 7:448–458. 2010. View Article : Google Scholar : PubMed/NCBI
2	Altekruse SF, McGlynn KA and Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 27:1485–1491. 2009. View Article : Google Scholar : PubMed/NCBI
3	Jelic S and Sotiropoulos G: Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 21:v59–v64. 2010. View Article : Google Scholar : PubMed/NCBI
4	Lu J, Getz G, Miska EA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
5	Croce C, Calin G and Volinia S: MicroRNA-based methods and compositions for the diagnosis and treatment of solid cancers Patent CN101389770A. 2012
6	Li A, Yu J, Kim H, et al: Serum miR-1290 as a marker of pancreatic cancer - response. Clin Cancer Res. 19:5252–5253. 2013. View Article : Google Scholar
7	Yuan Y, Shen Y, Xue L and Fan H: miR-140 suppresses tumor growth and metastasis of non-small cell lung cancer by targeting insulin-like growth factor 1 receptor. PloS One. 8:e736042013. View Article : Google Scholar : PubMed/NCBI
8	Gregory RI and Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res. 65:3509–3512. 2005. View Article : Google Scholar : PubMed/NCBI
9	Lynam-Lennon N, Maher SG and Reynolds JV: The roles of microRNA in cancer and apoptosis. Biol Rev. 84:55–71. 2009. View Article : Google Scholar : PubMed/NCBI
10	Li M, Li J, Ding X, He M and Cheng S-Y: microRNA and cancer. AAPS J. 12:309–317. 2010. View Article : Google Scholar
11	Liu N, Jiang N, Guo R, et al: MiR-451 inhibits cell growth and invasion by targeting MIF and is associated with survival in nasopharyngeal carcinoma. Mol Cancer. 12:1232013. View Article : Google Scholar : PubMed/NCBI
12	Wang T, Zang W-Q, Li M, Wang N, Zheng Y-l and Zhao G-Q: Effect of miR-451 on the biological behavior of the esophageal carcinoma cell line EC9706. Dig Dis Sci. 58:706–714. 2013. View Article : Google Scholar : PubMed/NCBI
13	Tian Y, Nan Y, Han L, et al: MicroRNA miR-451 downregulates the PI3K/AKT pathway through CAB39 in human glioma. Int J Oncol. 40:1105–1112. 2012.PubMed/NCBI
14	Nan Y, Han L, Zhang A, et al: MiRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res. 1359:14–21. 2010. View Article : Google Scholar : PubMed/NCBI
15	Sakamoto Y, Mafune K, Mori M, et al: Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma. Int J Oncol. 17:237–243. 2000.PubMed/NCBI
16	Chen R, Cui J, Xu C, Xue T, Guo K, Gao D, Liu Y, Ye S and Ren Z: The significance of MMP-9 over MMP-2 in HCC invasiveness and recurrence of hepatocellular carcinoma after curative resection. Ann Surg Oncol. 19(Suppl): S375–S384. 2012. View Article : Google Scholar : PubMed/NCBI
17	Lakka SS, Gondi CS, Yanamandra N, et al: Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene. 23:4681–4689. 2004. View Article : Google Scholar : PubMed/NCBI
18	Bushati N and Cohen SM: microRNA functions. Annu Rev Cell Dev Biol. 23:175–205. 2007. View Article : Google Scholar
19	Alvarez-Garcia I and Miska EA: MicroRNA functions in animal development and human disease. Development. 132:4653–4662. 2005. View Article : Google Scholar : PubMed/NCBI
20	Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST and Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 133:647–658. 2007. View Article : Google Scholar : PubMed/NCBI
21	Wang L, Yao J, Shi X, et al: MicroRNA-302b suppresses cell proliferation by targeting EGFR in human hepatocellular carcinoma SMMC-7721 cells. BMC Cancer. 13:4482013. View Article : Google Scholar : PubMed/NCBI
22	Nautiyal J, Banerjee S, Kanwar SS, et al: Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Oncol. 128:951–961. 2011.PubMed/NCBI
23	Liu Z-H, He Y-P and Qin H: The growth-inhibition effect of tamoxifen in the combination chemotherapeutics on the human cholangiocarcinoma cell line QBC939. Mol Biol Rep. 37:2693–2701. 2010. View Article : Google Scholar : PubMed/NCBI
24	Liu E, Kuang Y, He W, Xing X and Gu J: Casticin induces human glioma cell death through apoptosis and mitotic arrest. Cell Physiol Biochem. 31:805–814. 2013. View Article : Google Scholar : PubMed/NCBI
25	D’Amelio M, Sheng M and Cecconi F: Caspase-3 in the central nervous system: beyond apoptosis. Trends Neurosci. 35:700–709. 2012.
26	Ying TH, Yang SF, Tsai SJ, et al: Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway. Arch Toxicol. 86:263–273. 2012. View Article : Google Scholar : PubMed/NCBI
27	Persad R, Liu C, Wu T-T, et al: Overexpression of caspase-3 in hepatocellular carcinomas. Mod Pathol. 17:861–867. 2004. View Article : Google Scholar : PubMed/NCBI
28	Bandres E, Bitarte N, Arias F, et al: microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res. 15:2281–2290. 2009. View Article : Google Scholar : PubMed/NCBI
29	Kessenbrock K, Plaks V and Werb Z: Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 141:52–67. 2010. View Article : Google Scholar : PubMed/NCBI
30	Gialeli C, Theocharis AD and Karamanos NK: Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J. 278:16–27. 2011. View Article : Google Scholar : PubMed/NCBI
31	Leifler KS, Svensson S, Abrahamsson A, et al: Inflammation induced by MMP-9 enhances tumor regression of experimental breast cancer. J Immunol. 190:4420–4430. 2013. View Article : Google Scholar : PubMed/NCBI
32	Lee L-Y, Wu C-M, Wang C-C, et al: Expression of matrix metalloproteinases MMP-2 and MMP-9 in gastric cancer and their relation to claudin-4 expression. Histol Histopathol. 23:515–521. 2008.PubMed/NCBI
33	Roomi M, Monterrey J, Kalinovsky T, Rath M and Niedzwiecki A: Patterns of MMP-2 and MMP-9 expression in human cancer cell lines. Oncol Rep. 21:1323–1333. 2009.PubMed/NCBI
34	Piao S, Zhao S, Guo F, et al: Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma. J Cancer Res Clin Oncol. 138:627–635. 2012. View Article : Google Scholar : PubMed/NCBI