miR-96-5p regulates cervical cancer cell resistance to cisplatin by inhibiting lncRNA TRIM52-AS1 and promoting IGF2BP2

Kaohsiung J Med Sci. 2022 Dec;38(12):1178-1189. doi: 10.1002/kjm2.12593. Epub 2022 Nov 10.

Abstract

MicroRNA (miRNA) and long noncoding RNA (lncRNA) are both regulators of cancer progression. This study sought to discuss the functional mechanism of miR-96-5p/lncRNA TRIM52 antisense RNA 1 (head-to-head; TRIM52-AS1) in cervical cancer (CC) cell resistance to cisplatin (DDP). DDP-resistant CC cell line was established using increasing concentrations of DDP, followed by transfection with miR-96-5p inhibitor, or si-TRIM52-AS1, or insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) overexpression vector. Expression levels of miR-96-5p, TRIM52-AS1, and IGF2BP2 were determined. Changes in IC50 value to DDP, cell proliferation, and apoptosis rate were evaluated by cell-counting kit-8 assay, colony formation, and flow cytometry. The bindings of miR-96-5p to IGF2BP2 and TRIM52-AS1 to IGF2BP2 were verified by dual-luciferase or RNA pull-down assays. These experiments revealed an up-expression of miR-96-5p and IGF2BP2 while an under-expression of TRIM52-AS1 in CC cells. After DDP treatment, miR-96-5p inhibition increased apoptosis and decreased proliferation and DDP resistance. miR-96-5p bound to TRIM52-AS1 and downregulated TRIM52-AS1 expression, and TRIM52-AS1 bound to IGF2BP2 to inhibit IGF2BP2 expression. TRIM52-AS1 inhibition or IGF2BP2 overexpression neutralized the inhibition of silencing miR-96-5p on CC cell resistance to DDP. Overall, miR-96-5p improved CC cell resistance to DDP by inhibiting TRIM52-AS1 and promoting IGF2BP2.

Keywords: IGF2BP2; cervical cancer; cisplatin; lncRNA TRIM52-AS1.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA-Binding Proteins / genetics
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism

Substances

  • RNA, Long Noncoding
  • Cisplatin
  • MicroRNAs
  • IGF2BP2 protein, human
  • RNA-Binding Proteins
  • MIRN96 microRNA, human