Skip to main content
Top
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma

Authors: Zhao Sun, Changting Meng, Shihua Wang, Na Zhou, Mei Guan, Chunmei Bai, Shan Lu, Qin Han, Robert Chunhua Zhao

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

The aberrant expression of microRNAs has been demonstrated to play a crucial role in the initiation and progression of hepatocarcinoma. miR-1246 expression in High invasive ability cell line than significantly higher than that in low invasive ability cell line.

Methods

Transwell chambers (8-uM pore size; Costar) were used in the in vitro migration and invison anssay. Dual luciferase reporter gene construct and Dual luciferase reporter assay to identify the target of miR-1246. CADM1 expression was evaluated by immunohistochemistric staining. The clinical manifestations, treatments and survival were collected for statistical analysis.

Results

Inhibition of miR-1246 effectively reduced migration and invasion of hepatocellular carcinoma cell lines. Bioinformatics and luciferase reporter assay revealed that miR-1246 specifically targeted the 3′-UTR of Cell adhesion molecule 1 and regulated its expression. Down-regulation of CADM1 enhanced migration and invasion of HCC cell lines. Furthermore, in tumor tissues obtained from liver cancer patients, the expression of miR-1246 was negatively correlated with CADM1 and the high expression of miR-1246 combined with low expression of CADM1 might serve as a risk factor for stage1 liver cancer patients.

Conclusions

Our study showed that miR-1246, by down-regulation CADM1, enhances migration and invasion in HCC cells.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010, 127: 2893-2917.CrossRefPubMed Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010, 127: 2893-2917.CrossRefPubMed
2.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90.CrossRefPubMed
4.
go back to reference Baer C, Claus R, Plass C: Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res. 2013, 73: 473-477.CrossRefPubMed Baer C, Claus R, Plass C: Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res. 2013, 73: 473-477.CrossRefPubMed
5.
go back to reference Shen J, Stass SA, Jiang F: MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett. 2013, 329: 125-136.CrossRefPubMed Shen J, Stass SA, Jiang F: MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett. 2013, 329: 125-136.CrossRefPubMed
6.
go back to reference Giordano S, Columbano A: MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma?. Hepatology. 2013, 57: 840-847.CrossRefPubMed Giordano S, Columbano A: MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma?. Hepatology. 2013, 57: 840-847.CrossRefPubMed
7.
go back to reference Kutas P, Feckova L, Rehakova A, Novakova R, Homerova D, Mingyar E, Rezuchova B, Sevcikova B, Kormanec J: Strict control of auricin production in Streptomyces aureofaciens CCM 3239 involves a feedback mechanism. Appl Microbiol Biotechnol. 2013, 97: 2413-2421.CrossRefPubMed Kutas P, Feckova L, Rehakova A, Novakova R, Homerova D, Mingyar E, Rezuchova B, Sevcikova B, Kormanec J: Strict control of auricin production in Streptomyces aureofaciens CCM 3239 involves a feedback mechanism. Appl Microbiol Biotechnol. 2013, 97: 2413-2421.CrossRefPubMed
8.
go back to reference Shen Q, Cicinnati VR, Zhang X, Iacob S, Weber F, Sotiropoulos GC, Radtke A, Lu M, Paul A, Gerken G, Beckebaum S: Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion. Mol Cancer. 2010, 9: 227-CrossRefPubMedPubMedCentral Shen Q, Cicinnati VR, Zhang X, Iacob S, Weber F, Sotiropoulos GC, Radtke A, Lu M, Paul A, Gerken G, Beckebaum S: Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion. Mol Cancer. 2010, 9: 227-CrossRefPubMedPubMedCentral
9.
go back to reference Wu L, Cai C, Wang X, Liu M, Li X, Tang H: MicroRNA-142-3p, a new regulator of RAC1, suppresses the migration and invasion of hepatocellular carcinoma cells. FEBS Lett. 2011, 585: 1322-1330.CrossRefPubMed Wu L, Cai C, Wang X, Liu M, Li X, Tang H: MicroRNA-142-3p, a new regulator of RAC1, suppresses the migration and invasion of hepatocellular carcinoma cells. FEBS Lett. 2011, 585: 1322-1330.CrossRefPubMed
10.
go back to reference Bae HJ, Noh JH, Kim JK, Eun JW, Jung KH, Kim MG, Chang YG, Shen Q, Kim SJ, Park WS, Lee JY, Nam SW: MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene. 2014, 33: 2557-2567.CrossRefPubMed Bae HJ, Noh JH, Kim JK, Eun JW, Jung KH, Kim MG, Chang YG, Shen Q, Kim SJ, Park WS, Lee JY, Nam SW: MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene. 2014, 33: 2557-2567.CrossRefPubMed
11.
go back to reference Xu XL, Xing BC, Han HB, Zhao W, Hu MH, Xu ZL, Li JY, Xie Y, Gu J, Wang Y, Zhang ZQ: The properties of tumor-initiating cells from a hepatocellular carcinoma patient’s primary and recurrent tumor. Carcinogenesis. 2010, 31: 167-174.CrossRefPubMed Xu XL, Xing BC, Han HB, Zhao W, Hu MH, Xu ZL, Li JY, Xie Y, Gu J, Wang Y, Zhang ZQ: The properties of tumor-initiating cells from a hepatocellular carcinoma patient’s primary and recurrent tumor. Carcinogenesis. 2010, 31: 167-174.CrossRefPubMed
12.
go back to reference Xu X, Xing B, Hu M, Xu Z, Xie Y, Dai G, Gu J, Wang Y, Zhang Z: Recurrent hepatocellular carcinoma cells with stem cell-like properties: possible targets for immunotherapy. Cytotherapy. 2010, 12: 190-200.CrossRefPubMed Xu X, Xing B, Hu M, Xu Z, Xie Y, Dai G, Gu J, Wang Y, Zhang Z: Recurrent hepatocellular carcinoma cells with stem cell-like properties: possible targets for immunotherapy. Cytotherapy. 2010, 12: 190-200.CrossRefPubMed
13.
go back to reference Sun Z, Han Q, Zhou N, Wang S, Lu S, Bai C, Zhao RC: MicroRNA-9 enhances migration and invasion through KLF17 in hepatocellular carcinoma. Mol Oncol. 2013, 7: 884-894.CrossRefPubMed Sun Z, Han Q, Zhou N, Wang S, Lu S, Bai C, Zhao RC: MicroRNA-9 enhances migration and invasion through KLF17 in hepatocellular carcinoma. Mol Oncol. 2013, 7: 884-894.CrossRefPubMed
14.
go back to reference Li ZY, Xi Y, Zhu WN, Zeng C, Zhang ZQ, Guo ZC, Hao DL, Liu G, Feng L, Chen HZ, Chen F, Lv X, Liu DP, Liang CC: Positive regulation of hepatic miR-122 expression by HNF4alpha. J Hepatol. 2011, 55: 602-611.CrossRefPubMed Li ZY, Xi Y, Zhu WN, Zeng C, Zhang ZQ, Guo ZC, Hao DL, Liu G, Feng L, Chen HZ, Chen F, Lv X, Liu DP, Liang CC: Positive regulation of hepatic miR-122 expression by HNF4alpha. J Hepatol. 2011, 55: 602-611.CrossRefPubMed
15.
go back to reference Faraji F, Pang Y, Walker RC, Nieves BR, Yang L, Hunter KW: Cadm1 is a metastasis susceptibility gene that suppresses metastasis by modifying tumor interaction with the cell-mediated immunity. PLoS Genet. 2012, 8: e1002926-CrossRefPubMedPubMedCentral Faraji F, Pang Y, Walker RC, Nieves BR, Yang L, Hunter KW: Cadm1 is a metastasis susceptibility gene that suppresses metastasis by modifying tumor interaction with the cell-mediated immunity. PLoS Genet. 2012, 8: e1002926-CrossRefPubMedPubMedCentral
16.
go back to reference Mazumder ID, Mitra S, Roy A, Mondal RK, Basu PS, Roychoudhury S, Chakravarty R, Panda CK: Alterations of ATM and CADM1 in chromosomal 11q22.3-23.2 region are associated with the development of invasive cervical carcinoma. Hum Genet. 2011, 130: 735-748.CrossRef Mazumder ID, Mitra S, Roy A, Mondal RK, Basu PS, Roychoudhury S, Chakravarty R, Panda CK: Alterations of ATM and CADM1 in chromosomal 11q22.3-23.2 region are associated with the development of invasive cervical carcinoma. Hum Genet. 2011, 130: 735-748.CrossRef
17.
go back to reference Murakami Y: Functional cloning of a tumor suppressor gene, TSLC1, in human non-small cell lung cancer. Oncogene. 2002, 21: 6936-6948.CrossRefPubMed Murakami Y: Functional cloning of a tumor suppressor gene, TSLC1, in human non-small cell lung cancer. Oncogene. 2002, 21: 6936-6948.CrossRefPubMed
18.
go back to reference van den Berg RM, Snijders PJ, Grunberg K, Kooi C, Spreeuwenberg MD, Meijer CJ, Postmus PE, Smit EF, Steenbergen RD: Comprehensive CADM1 promoter methylation analysis in NSCLC and normal lung specimens. Lung Cancer. 2011, 72: 316-321.CrossRefPubMed van den Berg RM, Snijders PJ, Grunberg K, Kooi C, Spreeuwenberg MD, Meijer CJ, Postmus PE, Smit EF, Steenbergen RD: Comprehensive CADM1 promoter methylation analysis in NSCLC and normal lung specimens. Lung Cancer. 2011, 72: 316-321.CrossRefPubMed
19.
go back to reference Kikuchi S, Yamada D, Fukami T, Maruyama T, Ito A, Asamura H, Matsuno Y, Onizuka M, Murakami Y: Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma. Cancer. 2006, 106: 1751-1758.CrossRefPubMed Kikuchi S, Yamada D, Fukami T, Maruyama T, Ito A, Asamura H, Matsuno Y, Onizuka M, Murakami Y: Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma. Cancer. 2006, 106: 1751-1758.CrossRefPubMed
20.
go back to reference Takahashi Y, Iwai M, Kawai T, Arakawa A, Ito T, Sakurai-Yageta M, Ito A, Goto A, Saito M, Kasumi F, Murakami Y: Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer. Breast Cancer. 2012, 19: 242-252.CrossRefPubMed Takahashi Y, Iwai M, Kawai T, Arakawa A, Ito T, Sakurai-Yageta M, Ito A, Goto A, Saito M, Kasumi F, Murakami Y: Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer. Breast Cancer. 2012, 19: 242-252.CrossRefPubMed
21.
go back to reference Apostolidou S, Hadwin R, Burnell M, Jones A, Baff D, Pyndiah N, Mould T, Jacobs IJ, Beddows S, Kocjan G, Widschwendter M: DNA methylation analysis in liquid-based cytology for cervical cancer screening. Int J Cancer. 2009, 125: 2995-3002.CrossRefPubMed Apostolidou S, Hadwin R, Burnell M, Jones A, Baff D, Pyndiah N, Mould T, Jacobs IJ, Beddows S, Kocjan G, Widschwendter M: DNA methylation analysis in liquid-based cytology for cervical cancer screening. Int J Cancer. 2009, 125: 2995-3002.CrossRefPubMed
22.
go back to reference Overmeer RM1, Henken FE, Snijders PJ, Claassen-Kramer D, Berkhof J, Helmerhorst TJ, Heideman DA, Wilting SM, Murakami Y, Ito A, Meijer CJ, Steenbergen RD: Association between dense CADM1 promoter methylation and reduced protein expression in high-grade CIN and cervical SCC. J Pathol. 2008, 215: 388-397.CrossRefPubMed Overmeer RM1, Henken FE, Snijders PJ, Claassen-Kramer D, Berkhof J, Helmerhorst TJ, Heideman DA, Wilting SM, Murakami Y, Ito A, Meijer CJ, Steenbergen RD: Association between dense CADM1 promoter methylation and reduced protein expression in high-grade CIN and cervical SCC. J Pathol. 2008, 215: 388-397.CrossRefPubMed
23.
go back to reference Li QJ, Zhou L, Yang F, Wang GX, Zheng H, Wang DS, He Y, Dou KF: MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells. Tumour Biol. 2012, 33: 1455-1465.CrossRefPubMed Li QJ, Zhou L, Yang F, Wang GX, Zheng H, Wang DS, He Y, Dou KF: MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells. Tumour Biol. 2012, 33: 1455-1465.CrossRefPubMed
24.
go back to reference Zhang W, Zhou L, Ding SM, Xie HY, Xu X, Wu J, Chen QX, Zhang F, Wei BJ, Eldin AT, Zheng SS: Aberrant methylation of the CADM1 promoter is associated with poor prognosis in hepatocellular carcinoma treated with liver transplantation. Oncol Rep. 2011, 25: 1053-1062.PubMed Zhang W, Zhou L, Ding SM, Xie HY, Xu X, Wu J, Chen QX, Zhang F, Wei BJ, Eldin AT, Zheng SS: Aberrant methylation of the CADM1 promoter is associated with poor prognosis in hepatocellular carcinoma treated with liver transplantation. Oncol Rep. 2011, 25: 1053-1062.PubMed
25.
go back to reference Chen PJ, Yeh SH, Liu WH, Lin CC, Huang HC, Chen CL, Chen DS, Chen PJ: Androgen pathway stimulates microRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis. Hepatology. 2012, 56: 632-643.CrossRefPubMed Chen PJ, Yeh SH, Liu WH, Lin CC, Huang HC, Chen CL, Chen DS, Chen PJ: Androgen pathway stimulates microRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis. Hepatology. 2012, 56: 632-643.CrossRefPubMed
26.
go back to reference Baraniskin A, Nopel-Dunnebacke S, Ahrens M, Jensen SG, Zollner H, Maghnouj A, Wos A, Mayerle J, Munding J, Kost D, Reinacher-Schick A, Liffers S, Schroers R, Chromik AM, Meyer HE, Uhl W, Klein-Scory S, Weiss FU, Stephan C, Schwarte-Waldhoff I, Lerch MM, Tannapfel A, Schmiegel W, Andersen CL, Hahn SA: Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma. Int J Cancer. 2013, 132: E48-E57.CrossRefPubMed Baraniskin A, Nopel-Dunnebacke S, Ahrens M, Jensen SG, Zollner H, Maghnouj A, Wos A, Mayerle J, Munding J, Kost D, Reinacher-Schick A, Liffers S, Schroers R, Chromik AM, Meyer HE, Uhl W, Klein-Scory S, Weiss FU, Stephan C, Schwarte-Waldhoff I, Lerch MM, Tannapfel A, Schmiegel W, Andersen CL, Hahn SA: Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma. Int J Cancer. 2013, 132: E48-E57.CrossRefPubMed
27.
go back to reference Takeshita N, Hoshino I, Mori M, Akutsu Y, Hanari N, Yoneyama Y, Ikeda N, Isozaki Y, Maruyama T, Akanuma N, Komatsu A, Jitsukawa M, Matsubara H: Serum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma. Br J Cancer. 2013, 108: 644-652.CrossRefPubMedPubMedCentral Takeshita N, Hoshino I, Mori M, Akutsu Y, Hanari N, Yoneyama Y, Ikeda N, Isozaki Y, Maruyama T, Akanuma N, Komatsu A, Jitsukawa M, Matsubara H: Serum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma. Br J Cancer. 2013, 108: 644-652.CrossRefPubMedPubMedCentral
28.
go back to reference He G, Lei W, Wang S, Xiao R, Guo K, Xia Y, Zhou X, Zhang K, Liu X, Wang Y: Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth. J Cancer Res Clin Oncol. 2012, 138: 657-670.CrossRefPubMed He G, Lei W, Wang S, Xiao R, Guo K, Xia Y, Zhou X, Zhang K, Liu X, Wang Y: Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth. J Cancer Res Clin Oncol. 2012, 138: 657-670.CrossRefPubMed
Metadata
Title
MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma
Authors
Zhao Sun
Changting Meng
Shihua Wang
Na Zhou
Mei Guan
Chunmei Bai
Shan Lu
Qin Han
Robert Chunhua Zhao
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-616

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine