miR‑374c‑5p regulates PTTG1 and inhibits cell growth and metastasis in hepatocellular carcinoma by regulating epithelial‑mesenchymal transition

Mol Med Rep. 2022 Apr;25(4):148. doi: 10.3892/mmr.2022.12664. Epub 2022 Mar 2.

Abstract

A large number of studies have reported that microRNA (miR)‑374c‑5p plays an important role in the occurrence and development of malignant tumors, but there is no research on the role of miR‑374c‑5p in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of miR‑374c‑5p in HCC and the underlying molecular mechanism. The expression of miR‑374c‑5p in HCC tissues and HCC cell lines was analyzed via reverse transcription‑quantitative PCR. The association between miR‑374c‑5p and clinical pathology was also analyzed in patients with HCC. Kaplan‑Meier analysis and Cox multivariate analysis were used to evaluate the prognostic significance of miR‑374c‑5p in HCC. The biological functions of miR‑374c‑5p, including cell proliferation, migration and invasion and its potential molecular mechanism were analyzed in vivo and in vitro. In addition, the molecular mechanism of miR‑374c‑5p in HCC was further explored. The results demonstrated that miR‑374c‑5p expression was lower in HCC than in matched adjacent tissue samples. Patients with low expression of miR‑374c‑5p had poor prognosis and short survival time. Overexpression of miR‑374c‑5p inhibited HCC cell proliferation, migration and invasion in vitro. In vivo, it was found that overexpression of miR‑374c‑5p significantly inhibited the growth and proliferation of HCC cells. Dual‑luciferase reporter assays verified that miR‑374c‑5p directly targets the 3'‑untranslated region of pituitary tumor‑transforming 1 (PTTG1) and regulates PTTG1 expression. In general, it was revealed that miR‑374c‑5p regulates the malignant biological behavior of HCC through PTTG1, thereby affecting epithelial‑mesenchymal transition. Thus, miR‑374c‑5p is a potential biological indicator to predict poor prognosis in patients with HCC.

Keywords: cell growth and metastasis; epithelial-mesenchymal transition; hepatocellular carcinoma; microRNA‑374c‑5p; pituitary tumor-transforming 1.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • MicroRNAs* / genetics
  • Securin* / genetics

Substances

  • MIRN374 microRNA 374, human
  • MicroRNAs
  • Securin
  • pituitary tumor-transforming protein 1, human

Grants and funding

The present study was supported by Sichuan Provincial Department of Education, (grant no. 16TDD00025), the Popularization and Application Project of Sichuan Health Commission (grant no. 20PJ149), the Scientific Research Project of Affiliated Hospital of North Sichuan Medical College (grant no. 2020ZD001), the Scientific Research Project of Affiliated Hospital of North Sichuan Medical College (grant no. 2020JC035), the Cooperation Project Between Nanchong City and North Sichuan Medical College (grant nos. 19SXHZ0290 and 20SXQT0026), the Free Exploring Basic Research Project of Science and Technology of Sichuan province (grant no. 2020YJ0186) and the National Natural Science Foundation of China (grant no. 82003147).