LncRNA TRPM2-AS promotes ovarian cancer progression and cisplatin resistance by sponging miR-138-5p to release SDC3 mRNA

Aging (Albany NY). 2021 Feb 17;13(5):6832-6848. doi: 10.18632/aging.202541. Epub 2021 Feb 17.

Abstract

The role of TRPM2-AS lncRNA in OvC has not been explored. This study aimed to investigate whether and how TRPM2-AS contributes to the progression of OvC. First, qRT-PCR was employed to measure the expression of TRPM2-AS, miR-138-5p and SDC3 in OvC samples. A xenograft formation assay was subsequently performed to detect the tumor growth in vivo. The cell viability, colony formation, cell migration, cell invasion and cell apoptosis were later evaluated using a series of experiments. The western blot assay was utilized to detect the SDC3 protein expression and cell-apoptosis markers. Luciferase reporter gene assay, RIP, and RNA pull-down assays were performed to identify the association between TRPM2-AS, miR-138-5p and SDC3. Findings indicated that the expression of TRPM2-AS and SDC3 was significantly upregulated in OvC tissues and cells, while miR-138-5p expression was significantly downregulated in OvC samples. Unlike miR-138-5p, TRPM2-AS and SDC3 were found to promote OvC development. It was also found that TRPM2-AS could sponge miR-138-5p to release SDC3, thus promoting OvC progression. Apart from that, we discovered that both sh-TRPM2-AS and cisplatin could enhance the apoptosis of OvC cells. Overall, our findings suggested that the TRPM2-AS/miR-138-5p/SDC3 axis was closely associated with OvC tumorigenesis and cisplatin resistance.

Keywords: SDC3; TRPM2-AS; lncRNAs; miR-138-5p; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Carcinogenesis / genetics
  • Cisplatin / pharmacology
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • MicroRNAs / metabolism*
  • Middle Aged
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / metabolism*
  • Syndecan-3 / genetics*
  • Syndecan-3 / metabolism
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • MIRN138 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • SDC3 protein, human
  • Syndecan-3
  • TRPM Cation Channels
  • TRPM2 protein, human
  • Cisplatin