Knockdown of lncRNA MALAT1 induces pyroptosis by regulating the miR‑124/SIRT1 axis in cervical cancer cells

Int J Oncol. 2023 Dec;63(6):138. doi: 10.3892/ijo.2023.5586. Epub 2023 Nov 3.

Abstract

The aim of the present study was to elucidate the role and downstream mechanism of long non‑coding RNA (lncRNA) metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) in the process of cervical cancer cell pyroptosis. The effect of inhibiting lncRNA MALAT1 on cervical cancer cells was determined using primary cells isolated from patients and U14 cervical tumor‑bearing nude mice. The level of lncRNA MALAT1 expression and cell viability were determined for relationship analysis. Pyroptosis was then investigated in HeLa cells with lncRNA MALAT1 knockdown or overexpression with or without lipopolysaccharide (LPS) treatment. Bioinformatics tools were used to identify downstream factors of lncRNA MALAT1, which were subsequently verified by gain‑ or loss‑of‑function analyses in the process of cervical cancer cell pyroptosis. It was observed that the level of lncRNA MALAT1 was markedly higher in cervical carcinoma cells compared with expression in paracarcinoma cells, and knockdown of lncRNA MALAT1 induced cervical cancer cell death through pyroptosis. By contrast, overexpression of lncRNA MALAT1 blocked LPS‑induced pyroptosis. These results, combined with bioinformatics statistical tools, demonstrated that the microRNA (miR)‑124/sirtuin 1 (SIRT1) axis may affect the progression of cervical cancer at least partly by mediating the effect of lncRNA MALAT1 on the pyroptosis of cervical cancer cells. In conclusion, the lncRNA MALAT1/miR‑124/SIRT1 regulatory axis in cervical cancer cells may mediate pyroptosis and may provide potential targets against the progression of cervical cancer.

Keywords: cervical carcinoma; long non‑coding RNA metastasis‑associated lung adenocarcinoma transcript 1; microRNA‑124; pyroptosis; sirtuin 1.

MeSH terms

  • Animals
  • Female
  • HeLa Cells
  • Humans
  • Lipopolysaccharides
  • Mice
  • Mice, Nude
  • MicroRNAs* / metabolism
  • Pyroptosis / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Sirtuin 1 / genetics
  • Sirtuins*
  • Uterine Cervical Neoplasms* / genetics

Substances

  • RNA, Long Noncoding
  • Sirtuin 1
  • Sirtuins
  • Lipopolysaccharides
  • MicroRNAs
  • SIRT1 protein, human
  • MIRN124 microRNA, human
  • Mirn124 microRNA, mouse