Xiao Wang 1 , 2 , Shasha Liu 1 , 3 , Ling Cao 1 , 2 , Tengfei Zhang 1 , Dongli Yue 1 , 2 , Liping Wang 2 , Yu Ping 1 , 3 , Qianyi He 2 , Chaoqi Zhang 1 , 2 , Meng Wang 1 , Xinfeng Chen 1 , 2 , Qun Gao 1 , 2 , Dan Wang 1 , 2 , Zhen Zhang 1 , Fei Wang 1 , Li Yang 1 , Jieyao Li 1 , 2 , Lan Huang 1 , Bin Zhang 4 , Yi Zhang 1 , 2 , 3 , 5
23 September 2017
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.