lncRNA ENST00000422059 promotes cell proliferation and inhibits cell apoptosis in breast cancer by regulating the miR-145-5p/KLF5 axis

Acta Biochim Biophys Sin (Shanghai). 2023 Dec 25;55(12):1892-1901. doi: 10.3724/abbs.2023226.

Abstract

Krüppel-like zinc-finger transcription factor 5 (KLF5) is a vital regulator of breast cancer (BC) onset and progression. The mechanism by which KLF5 regulates BC is still not clearly known. In this study, bioinformatics analysis shows that BC-affected individuals with elevated KLF5 expression levels have poor clinical outcomes. We further verify that miR-145-5p regulated KLF5 expression to promote cell apoptosis and inhibit cell proliferation in BC via dual-luciferase reporter assay, western blot analysis, qRT-PCR, CCK-8 assay and cell apoptosis assay. In addition, based on bioinformatics analysis, the binding of ENST00000422059 with miR-145-5p is confirmed by dual-luciferase reporter assay. Subsequently, FISH, western blot analysis, qRT-PCR, CCK-8 and cell apoptosis assays verified that ENST00000422059 increases KLF5 protein expression by sponging miRNA to promote cell proliferation and inhibit cell apoptosis. Finally, ENST00000422059 is found to accelerate tumor progression by regulating the miR-145-5p/KLF5 axis in vivo. In conclusion, this study suggests that ENST00000422059 upregulates KLF5 by sponging miR-145-5p to promote BC progression.

Keywords: ENST00000422059; KLF5; breast cancer; miR-145-5p.

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Luciferases / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Sincalide / metabolism
  • Transcription Factors / metabolism

Substances

  • RNA, Long Noncoding
  • Sincalide
  • MicroRNAs
  • Transcription Factors
  • Luciferases
  • KLF5 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN145 microRNA, human

Grants and funding

This work was supported by the grants from the Foundation of Noncoding RNA Transformation of Major Diseases of Anhui Key Universities (No. RNA202003), the Natural Science Foundation of Anhui (No. 2108085MH290), the Scientific Research Fund Project for Talent Introduction of Yijishan Hospital, Wannan Medical College (No. YR202116), and the Key Research Foundation of Wannan Medical College (No. WK2020ZF09), and the Major Natural Science Research Projects in Universities in Anhui Province (No. 2022AH040179).