Abstract

BackgroundHepatocellular carcinoma (HCC) is one of the most malignant tumor types and has a high incidence and mortality. Many miRNAs play important roles in the development of HCC. Identification of these miRNAs and their targets is increasingly urgent for a better understandingof miRNA function in both physiological and pathological contexts. Many studies have shown that the expression of let-7 is often downregulated in the process of tumorigenesis, suggesting that let-7 may participate in this process as an oncogene.MethodsImmunochemistry staining was used to observe the expression of let-7b in HCC tissues. A CCK-8 assay was employed to detect the role of let-7b in the proliferation of HCC cells. The cell cycle of HCC cells was examined by flow cytometry. BALB/c nu/nu mice were used to detect the tumorigenesis potential of HCC cells; western blot and real-time PCR were employed to observe the expression of p21 in HCC cells.ResultsIn our previous studies investigating HCC tissue samples obtained from the national tissue samples bank of liver cancer in Eastern Hepatobiliary Surgery Hospital, we found one abnormal expression of miRNA (let-7b), which was significantly downregulated in HCC tissue. In the current work, we studied the relationship between let-7b and HCC to potentially provide invaluable information for developing novel therapeutic strategies for treating HCC. Based on our findings, let-7b expression was absent in HCC tumors, and its lower expression was associated with poor prognosis of HCC. In further experiments, we found that let-7b inhibited HCC cell proliferation through upregulation of p21.ConclusionThe results of our study suggested that let-7b might inhibit the proliferation of HCC cells by upregulating p21.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the most malignant tumor types and has a high incidence and mortality

  • In our previous studies investigating HCC tissue samples from the national tissue samples bank of liver cancer in Eastern Hepatobiliary Surgery Hospital, we found one abnormal expression of miRNA, which was significantly downregulated in HCC tissue

  • Let‐7b expression in HCC tissues and the relationship with the prognosis of HCC patients To determine the expression of let-7 in the early stage of HCC, RT-PCR analysis was employed to assess the expression of let-7b in HCC and corresponding nontumor (NT) tissues

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most malignant tumor types and has a high incidence and mortality. Many miRNAs play important roles in the development of HCC. Identification of these miRNAs and their targets is increasingly urgent for a better understandingof miRNA function in both physiological and pathological contexts. The miRNA let-7 plays a vital role in tumor suppression in many cancers, including esophageal squamous cell carcinoma, lung cancer and prostate cancer [5,6,7]. Extensive evidence suggests that let-7 functions as a tumor suppressor by targeting multiple oncogenes and that a reduction in let-7 is strongly associated with increased tumorigenicity and poor prognosis in patients [7, 9]. The aberrant expression of let-7 is known to contribute to the development and progression of HCC

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