Abstract
Recently, microRNAs (miRNAs) have been acknowledged as important regulators of hepatocarcinogenesis and tumor progression. Therefore, identifying the underlying molecular mechanisms of miRNAs in the occurrence and development of hepatocellular carcinoma (HCC) may be important for understanding the pathogenesis of HCC and aid the identification of potential therapeutic strategies. In the present study, miRNA (miR)‑601 was significantly downregulated in HCC tissues and cell lines; low miR‑601 expression was strongly associated with tumor, node and metastasis staging and lymph node metastasis of patients with HCC. In addition, the overexpression of miR‑601 expression significantly inhibited the proliferation and invasion of HCC cells. Regarding the underlying mechanism, phosphoinositide‑3‑kinase regulatory subunit 3 (PIK3R3) was predicted to be a direct target of miR‑601 in HCC cells. Furthermore, restoration of PIK3R3 expression in these cells counteracted the inhibitory effects of miR‑601 on cell proliferation and invasion in HCC. Notably, miR‑601 overexpression inhibited the protein kinaseB(AKT)/mammalian target of rapamycin (mTOR) signaling pathway in HCC via the regulation of PIK3R3. Collectively, these results demonstrated that miR‑601 may inhibit the progression of HCC by directly targeting PIK3R3 and regulating the AKT/mTOR signaling pathway. Therefore, miR‑601 may be an effective therapeutic target for the treatment of patients with HCC.
Highlights
Hepatocellular carcinoma (HCC), accounting for >90% of all cases of primary liver cancer, ranks as the sixth most common type of cancer and the second leading cause of cancer‐associated mortality worldwide [1]
Reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) analysis demonstrated that miR‐601 was expressed at significantly lower levels in HCC tissues compared with the matched adjacent normal tissues (P
The results of the RT‐qPCR analysis in the present study demonstrated that miR‐601 expression was significantly downregulated in HCC tissues and cell lines
Summary
Hepatocellular carcinoma (HCC), accounting for >90% of all cases of primary liver cancer, ranks as the sixth most common type of cancer and the second leading cause of cancer‐associated mortality worldwide [1]. There are >1 million novel diagnosed HCC cases and ~1 million incidences of mortality that occur annually worldwide due to HCC [2,3]. Exposure to aflatoxin B1 and infection with hepatitis viruses B or C have been identified as two primary risk factors for HCC [4]. Surgical hepatectomy and liver transplantation remain the predominant treatments for patients with HCC [6]. Significant improvements in surgical techniques and perioperative management have been made; the outcomes of treatment for patients with HCC remain unsatisfactory with a 5‐year survival rate of
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