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 PMID:29156819  

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

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
Oncotarget | 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.

Pubmed ID: 29156819

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