miR-29a-3p suppresses cell proliferation and migration by downregulating IGF1R in hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane heterotetrameric protein that has been reported to promote transformation to malignancy and cancer cell proliferation and survival. In this study, we found that the expression of miR-29a-3p was downregulated in HCC patients, resulting in poor survival rates. Contrastingly, the overexpression of miR-29a-3p significantly inhibited proliferation and migration in HepG2 cells. miR-29a-3p directly targeted IGF1R and down-regulated its expression. Moreover, knockdown of IGF1R led to the increased production of chemokine ligand 5 (CCL5). In tumor lesions, the local expression of CCL5 negatively affected the expression of IGF1R. Transwell analysis showed that CCL5 was important for the chemotactic movement of CD8+ T lymphocytes. The expression of CCL5 in HCC tissues positively correlated with the expression of CD8+ T lymphocyte surface marker, CD8. Patients with high CCL5 expression exhibited better survival. Our results revealed that miR-29a-3p is a tumor suppressor gene that acts by directly repressing the oncogene IGF1R, which takes part in immunoregulation in tumor microenvironments in HCC, implying that miR-29a-3p could be a potential target for HCC treatment.

• Authors: Xiao Wang, Shasha Liu, Ling Cao, Tengfei Zhang, Dongli Yue, Liping Wang, Yu Ping, Qianyi He, Chaoqi Zhang, Meng Wang, Xinfeng Chen, Qun Gao, Dan Wang, Zhen Zhang, Fei Wang, Li Yang, Jieyao Li, Lan Huang, Bin Zhang, Yi Zhang
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 49 Pg. 86592-86603 (Oct 17 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 29156819 (Publication Type: Journal Article)