MicroRNA-572/hMOF/Sirt6 regulates the progression of ovarian cancer

Cell Cycle. 2020 Oct;19(19):2509-2518. doi: 10.1080/15384101.2020.1809258. Epub 2020 Aug 23.

Abstract

Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is involved in the pathogenesis of various cancers. This article aimed to reveal the potential mechanism of the miR-572/hMOF/Sirt6 axis in ovarian cancer (OC). In this study, we found that the mRNA and protein levels of hMOF and Sirt6 were abnormally down-regulated in OC tissues and cells. Further study indicated that the overexpression of hMOF increased the level of H4 histone acetylation in the Sirt6 promoter region and enhanced the ability of hMOF to bind to the Sirt6 promoter in OC cells, and repressed the proliferation of SKOV3 cells and promoted the apoptosis of SKOV3 cells via up-regulating Sirt6. Moreover, it was found that miR-572 negatively regulated hMOF luciferase activity. After the transfection of miR-572 inhibitor into SKOV3 cells, the cell proliferation was significantly repressed, while this repression was reversed after the transfection of shRNA-hMOF. Besides, the overexpression of hMOF could significantly inhibit the growth of tumors. Overall, our findings uncovered a novel regulatory pattern of hMOF in OC progression and provided new insights for relieving OC.

Keywords: Ovarian cancer; Sirt6; hMOF; miR-572; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism*
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Signal Transduction
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Tumor Burden

Substances

  • MIRN-572 microRNA, human
  • MicroRNAs
  • Histone Acetyltransferases
  • KAT8 protein, human
  • SIRT6 protein, human
  • Sirtuins

Grants and funding

This work was supported by Innovation Funds of The First Affiliated Hospital of Zhengzhou University [Grants2015CaiMB]; The National Nature Science Foundation of China [81802609]; ZhongYuan thousand talents program-the Zhongyuan eminent doctor in Henan province [ZYQR 201810107]; The Science and Technology Colleges Innovation Team Support Program of Henan Province [18IRTSTHN024].