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.

Investigation of miR-490-3p Expression in Hepatocellular Carcinoma Based on Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) and a Meta-Analysis of 749 Cases

“…Many studies have demonstrated that miRNAs are involved in various biological processes of HCC, such as cell proliferation, invasion, migration, and the cell cycle [ 9 , 32 , 33 ]. Additionally, miRNAs can act as diagnostic and prognostic biomarkers in HCC [ 34 , 35 ].…”

Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications

“…HS6ST3 could promote breast cancer cell proliferation by upregulating IGF1R expression (29). It has been shown that IGF1R inhibits CCL5 expression and consequently reduces the chemotactic movement of CD8 + T lymphocytes (30). Taken together these findings suggest that through IGF1R, HS6ST3 could affect both CCL5 levels and tumor infiltrating CD8 + T lymphocytes behavior.…”

“…HS6ST3 encodes a member of Heparan sulfate (HS) involved in several cellular and molecular processes, including cell proliferation and differentiation (28). By regulating IGFR1 expression, HS6ST3 could affect CCL5 expression (29,30).…”

Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients

“…MiR-16-5p was reportedly downregulated in breast cancer [76], hepatocellular carcinoma [77] and glioma [78], in agreement with our ndings. Overall, miR-29a-3p has been reported to function as a tumour suppressor and is downregulated in many types of cancers, such as thyroid carcinoma [32], colorectal carcinoma [79] and hepatocellular carcinoma [80].The downregulation of miR-34c-5p has been reported in several types of cancer, such as leukaemia [57] and osteosarcoma [58], and it has been closely associated with poor prognosis. Similarly, miR-490-5p is markedly downregulated in hepatocellular carcinoma tissues [81], in renal cell carcinoma tissues and cells [82] and in childhood neuroblastomas and cell lines [83].…”