MicroRNA-182 Downregulates Metastasis Suppressor 1 and Contributes to Metastasis of Hepatocellular Carcinoma

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2012 Jun 12

PMID 22681717

Citations 96

Authors

Jian Wang

Jingwu Li

Junling Shen

Chen Wang

Lili Yang

Xinwei Zhang

Affiliations

Soon will be listed here.

Abstract

Background: miR-182 is one of the most significantly up-regulated miRNAs in hepatocellular carcinoma (HCC). Metastasis suppressor 1 (MTSS1), one target gene of miR-182, plays an important role in the metastasis of cancers. However, it remains unclear what role does function and mechanism of miR-182 and MTSS1play in HCC.

Methods: miR-182 expression was tested in 86 cases of paired HCC and normal tissues by real-time PCR and the relationships between miR-182 expression and clinicopathological parameters were analyzed. The expression of MTSS1 was evaluated by immunohistochemistry and western blot in the above tissues and its correlation with miR-182 expression was analyzed. Moreover, western blot and invasion assays were performed after transfection of pre-miR-182 or anti-miR-182 to HCC cell lines. In addition, luciferase assays was performed to confirm the regulation of miR-182 on MTSS1.

Results: Compared with normal tissue, miR-182 was up-regulated and MTSS1 was down-regulated in HCC tissues. Moreover, the over-expression of miR-182 was correlated with intrahepatic metastasis (p = 0.034) and poor prognosis (p = 0.039) of HCC patients. There was a negative correlation between miR-182 and MTSS1 expression in both HCC tissues (r = -0.673, p < 0.01) and HCC cell lines (r = -0.931, p = 0.021). Furthermore, the up-regulation of miR-182 resulted in the down-regulation of MTSS1 and increased invasive potential of HUH-1, and reverse results were also confirmed when the expression of miR-182 was inhibited. In addition, the results of the luciferase assay demonstrated the targeted regulation of miR-182 on MTSS1.

Conclusions: miR-182 could promote metastasis of HCC and inhibit the expression of MTSS1. miR-182 and MTSS1 are potential prognostic markers and/or therapeutic targets in HCC.

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References

Liu K, Wang G, Ding H, Chen Y, Yu G, Wang J . Downregulation of metastasis suppressor 1(MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer. BMC Cancer. 2010; 10:428. PMC: 2928798. DOI: 10.1186/1471-2407-10-428. View

Nixdorf S, Grimm M, Loberg R, Marreiros A, Russell P, Pienta K . Expression and regulation of MIM (Missing In Metastasis), a novel putative metastasis suppressor gene, and MIM-B, in bladder cancer cell lines. Cancer Lett. 2004; 215(2):209-20. DOI: 10.1016/j.canlet.2004.05.002. View

Parr C, Jiang W . Metastasis suppressor 1 (MTSS1) demonstrates prognostic value and anti-metastatic properties in breast cancer. Eur J Cancer. 2009; 45(9):1673-83. DOI: 10.1016/j.ejca.2009.02.019. View

Nicoloso M, Spizzo R, Shimizu M, Rossi S, Calin G . MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer. 2009; 9(4):293-302. DOI: 10.1038/nrc2619. View

Lee Y, Macoska J, Korenchuk S, Pienta K . MIM, a potential metastasis suppressor gene in bladder cancer. Neoplasia. 2002; 4(4):291-4. PMC: 1531703. DOI: 10.1038/sj.neo.7900231. View

Law P, Wong N . Emerging roles of microRNA in the intracellular signaling networks of hepatocellular carcinoma. J Gastroenterol Hepatol. 2011; 26(3):437-49. DOI: 10.1111/j.1440-1746.2010.06512.x. View

Dai B, Meng J, Peyton M, Girard L, Bornmann W, Ji L . STAT3 mediates resistance to MEK inhibitor through microRNA miR-17. Cancer Res. 2011; 71(10):3658-68. PMC: 3392199. DOI: 10.1158/0008-5472.CAN-10-3647. View

Pollard T, Borisy G . Cellular motility driven by assembly and disassembly of actin filaments. Cell. 2003; 112(4):453-65. DOI: 10.1016/s0092-8674(03)00120-x. View

Schutte K, Bornschein J, Malfertheiner P . Hepatocellular carcinoma--epidemiological trends and risk factors. Dig Dis. 2009; 27(2):80-92. DOI: 10.1159/000218339. View

10.

Fan H, Chen T, Hsieh C, Jan H, His S, De-Chuan C . Liver transplantation is an alternative treatment of hepatocellular carcinoma beyond the Milan criteria. Am J Surg. 2010; 200(2):252-7. DOI: 10.1016/j.amjsurg.2009.07.049. View

11.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

12.

Yang Y, Nagano H, Ota H, Morimoto O, Nakamura M, Wada H . Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection. Surgery. 2007; 141(2):196-202. DOI: 10.1016/j.surg.2006.06.033. View

13.

Craig V, Cogliatti S, Imig J, Renner C, Neuenschwander S, Rehrauer H . Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood. 2011; 117(23):6227-36. PMC: 3790944. DOI: 10.1182/blood-2010-10-312231. View

14.

Ofir M, Hacohen D, Ginsberg D . MiR-15 and miR-16 are direct transcriptional targets of E2F1 that limit E2F-induced proliferation by targeting cyclin E. Mol Cancer Res. 2011; 9(4):440-7. DOI: 10.1158/1541-7786.MCR-10-0344. View

15.

Wang Y, Lee A, Ma J, Wang J, Ren J, Yang Y . Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target. J Biol Chem. 2008; 283(19):13205-15. DOI: 10.1074/jbc.M707629200. View

16.

Li Q, Wang J, Juzi J, Sun Y, Zheng H, Cui Y . Clonality analysis for multicentric origin and intrahepatic metastasis in recurrent and primary hepatocellular carcinoma. J Gastrointest Surg. 2008; 12(9):1540-7. DOI: 10.1007/s11605-008-0591-y. View

17.

Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N . Widespread changes in protein synthesis induced by microRNAs. Nature. 2008; 455(7209):58-63. DOI: 10.1038/nature07228. View

18.

Donnem T, Lonvik K, Eklo K, Berg T, Sorbye S, Al-Shibli K . Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer: coexpression with vascular endothelial growth factor-A predicts poor survival. Cancer. 2011; 117(14):3193-200. DOI: 10.1002/cncr.25907. View

19.

Patnaik S, Kannisto E, Knudsen S, Yendamuri S . Evaluation of microRNA expression profiles that may predict recurrence of localized stage I non-small cell lung cancer after surgical resection. Cancer Res. 2009; 70(1):36-45. DOI: 10.1158/0008-5472.CAN-09-3153. View

20.

Segura M, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S . Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci U S A. 2009; 106(6):1814-9. PMC: 2634798. DOI: 10.1073/pnas.0808263106. View