MicroRNA‑495 suppresses cell proliferation and invasion of hepatocellular carcinoma by directly targeting insulin‑like growth factor receptor‑1

Abstract

Abstract. Hepatocellular carcinoma (HCC) is the fifth most common malignancy and second-most frequent cause of cancer-associated deaths worldwide. Previously, increasing studies report that microRNAs (miRNAs/miRs) are abnormally expressed in various types of human cancers and may participate in the tumourigenesis and tumour development of HCC. miRNA-based targeted therapy is effective against different molecular targets and may increase the sensitisation of cancer cells to therapy by several folds. Therefore, further validation of potentially important miRNAs involved in HCC initiation and progression may provide valuable insights into the treatment of patients with HCC. miR-495 is abnormally expressed in multiple types of human cancers. However, the expression level and roles of miR-495 in HCC have yet to be completely elucidated. In the present study, miR-495 expression was frequently downregulated in HCC tissues and cell lines, and miR-495 expression levels were significantly correlated with tumour size, tumor-node-metastasis (TNM) stage and lymph node metastasis in patients with HCC. Functional assays revealed that miR-495 overexpression inhibited cell proliferation and invasion in HCC. Insulin-like growth factor receptor-1 (IGF1R) was identified as a direct target gene of miR-495 in HCC. IGF1R was upregulated in HCC tissues and negatively correlated with miR-495 expression level. The upregulation of IGF1R rescued the miR-495-induced tumour-suppressive roles in HCC cell proliferation and invasion, and the restored miR-495 expression inactivated the protein kinase B and extracellular regulated protein kinase signalling pathways in HCC. These results provide novel insights into the molecular mechanism underlying HCC progression, and suggest that miR-495 may be investigated as a novel therapeutic target for patients with this disease.

Retracted: LINC00707 contributes to hepatocellular carcinoma progression via sponging miR‐206 to increase CDK14

“…MiR‐144 can suppress ovarian cancer development by targeting RUNX1 (Han, Zhu, & Zhang, ). Additionally, miR‐495 can inhibit HCC cell progression by directly targeting IGF1 (Ye et al, ). MiR‐423 enhances HCC invasiveness through regulating BRMS1 (X.…”

Gene Therapy for Hepatocellular Carcinoma: An Update

“…Autophagy induction is a frequent response of HCC cells to chemotherapeutic drugs and induces acquired resistance. In the study by Ye Y et al [68] insulin-like growth factor receptor-1 (IGF1R) was identified as a direct target gene of miR-495 in hepatocellular carcinoma. Insulin-like growth factor receptor-1 was upregulated in hepatocellular tissues and negatively correlated with miR-495 expression level.…”

microRNA‐495 reduces visceral sensitivity in mice with diarrhea‐predominant irritable bowel syndrome through suppression of the PI3K/AKT signaling pathway via PKIB

“…In our study, we also verified the targeting relationship between PKIB and miR‐495. Besides, overexpressed miR‐495 suppresses proliferation and invasion of hepatocellular carcinoma cells, and inactivates the AKT and ERK signaling pathways in hepatocellular carcinoma cells . It is reported that the PI3K/AKT signaling pathway has also been shown to play a pro‐inflammatory role in intestinal diseases such as colitis .…”