LncRNA STARD7-AS1 suppresses cervical cancer cell proliferation while promoting autophagy by regulating miR-31-5p/TXNIP axis to inactivate the mTOR signaling

J Gynecol Oncol. 2024 Jul;35(4):e97. doi: 10.3802/jgo.2024.35.e97. Epub 2024 Apr 19.

Abstract

Objective: Cervical cancer (CC) is a serious gynecologic health issue for women worldwide. Long non-coding RNA (lncRNA) has been well-documented in controlling malignant behavior of various cancer cells. The role of lncRNA STARD7-AS1 in regulating CC cell proliferation and autophagy and its possible mechanism were investigated in this work.

Methods: RNA expression and protein levels were quantified by reverse transcription quantitative polymerase chain reaction and western blotting. The location of STARD7-AS1 in CC cells was examined using subcellular fraction assays. Cell Counting Kit-8 assays and colony forming assays were performed to measure CC cell viability and proliferation. Autophagy in CC cells was evaluated using macrophage-derived chemokine (MDC) staining and transmission electron microscopy. The binding between microRNA (miR)-31-5p and STARD7-AS1 (or thioredoxin-interacting protein [TXNIP]) was determined by performing luciferase reporter, RNA pull-down or RNA immunoprecipitation assays.

Results: STARD7-AS1 overexpression significantly suppressed CC cell viability and proliferation while notably inducing autophagy. STARD7-AS1 upregulated TXNIP expression via interaction with miR-31-5p. In addition, the effects of STARD7-AS1 on CC cell proliferation and autophagy were reversed by TXNIP silencing. The suppressive effect of STARD7-AS1 overexpression on phosphorylated levels of mTOR and S6K1 was countervailed by TXNIP deficiency.

Conclusion: In conclusion, lncRNA STARD7-AS1 inhibits CC cell proliferation and promotes cell autophagy by targeting the miR-31-5p/TXNIP axis to inactivate the mTOR signaling.

Keywords: Autophagy; Bioinformatics; Cervical Cancer; Competitive Endogenous RNA.

MeSH terms

  • Autophagy* / genetics
  • Carrier Proteins* / genetics
  • Carrier Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases* / metabolism
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • MIRN31 microRNA, human
  • TOR Serine-Threonine Kinases
  • MTOR protein, human
  • Carrier Proteins
  • TXNIP protein, human