Let-7g targets collagen type I α2 and inhibits cell migration in hepatocellular carcinoma

Ji, Junfang; Zhao, Lei; Budhu, Anuradha; Forgues, Marshonna; Jia, Hu-Liang; Qin, Lun-Xiu; Ye, Qing-Hai; Yu, Jinming; Shi, Xuetao; Tang, Zhao-You; Wang, Xin Wei

doi:10.1016/j.jhep.2009.12.025

« Previous Next »Journal of Hepatology
Volume 52, Issue 5 , Pages 690-697, May 2010

Let-7g targets collagen type I α2 and inhibits cell migration in hepatocellular carcinoma

Junfang Ji
- Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Cancer Institute, Bethesda, MD, USA
- These authors contributed equally to this work.
Lei Zhao
- Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Cancer Institute, Bethesda, MD, USA
- Shandong Provincial Tumour Hospital and Institute of Oncology, Jinan, China
- These authors contributed equally to this work.
Anuradha Budhu
- Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Cancer Institute, Bethesda, MD, USA
Marshonna Forgues
- Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Cancer Institute, Bethesda, MD, USA
Hu-Liang Jia
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
Lun-Xiu Qin
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
Qing-Hai Ye
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
Jinming Yu
- Shandong Provincial Tumour Hospital and Institute of Oncology, Jinan, China
Xuetao Shi
- Shandong Provincial Tumour Hospital and Institute of Oncology, Jinan, China
Zhao-You Tang
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
Xin Wei Wang
- Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Cancer Institute, Bethesda, MD, USA
- Corresponding author. Address: 37 Convent Dr., MSC 4258, Building 37, Room 3044A, Bethesda, MD 20892, USA. Tel.: +1 301 496 2099; fax: +1 301 496 0497.

Received 9 July 2009; received in revised form 3 December 2009; accepted 12 December 2009. published online 02 March 2010.

Background & Aims

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis mainly due to metastasis. MicroRNAs are endogenous small noncoding RNAs that regulate cellular gene expression and are functionally linked to tumourigenesis. Using microarray analysis, we recently identified 20 miRNAs associated with HCC metastasis. Here, we carried out further analyses on one of these microRNAs, let-7g, to determine whether it is functionally linked to HCC metastasis.

Methods

Quantitative real-time polymerase chain reaction was used to determine the level of mature let-7g transcript in HCC clinical specimens and its correlation with patient survival. Ectopic expression of let-7g was carried out in HCC cell lines to assess its influence on cell growth, migration, and invasion.

Results

We confirmed that the level of let-7g was significantly lower in metastatic HCCs compared to metastasis-free HCCs. Moreover, low let-7g expression in a tumour was predictive of poor survival in HCC patients. Functional studies indicated that ectopic expression of let-7g significantly inhibits HCC cell migration and cell growth. In-silico analysis revealed members of soluble collagens as potential targets of let-7g. Consistently, the levels of type I collagen α2 (COL1A2) and let-7g were inversely correlated in HCC clinical specimens. COL1A2 was experimentally validated as a direct target of let-7g. Moreover, addition of COL1A2 counteracted the inhibitory effect of let-7g on cell migration.