The LncRNA RP11-301G19.1/miR-582-5p/HMGB2 axis modulates the proliferation and apoptosis of multiple myeloma cancer cells via the PI3K/AKT signalling pathway

Cancer Gene Ther. 2022 Mar;29(3-4):292-303. doi: 10.1038/s41417-021-00309-5. Epub 2021 Mar 11.

Abstract

Long non-coding RNAs (lncRNAs) have recently been reported to act as crucial regulators and prognostic biomarkers of human tumorigenesis. Based on microarray data, RP11-301G19.1 was previously identified as an upregulated lncRNA during B cell development. However, the effect of RP11-301G19.1 on multiple myeloma (MM) cells remains unclear. In the present study, the effects of RP11-301G19.1 on tumour progression were ascertained both in vitro and in vivo. Our results demonstrated that RP11-301G19.1 was upregulated in MM cell lines and that its downregulation inhibited the proliferation and cell cycle progression and promoted the apoptosis of MM cells. Bioinformatic analysis and luciferase reporter assay results revealed that RP11-301G19.1 can upregulate the miR-582-5p-targeted gene HMGB2 as a competing endogenous RNA (ceRNA). Furthermore, Western blot results indicated that RP11-301G19.1 knockdown decreased the levels of PI3K and AKT phosphorylation without affecting their total protein levels. Additionally, in a xenograft model of human MM, RP11-301G19.1 knockdown significantly inhibited tumour growth by downregulating HMGB2. Overall, our data demonstrated that RP11-301G19.1 is involved in MM cell proliferation by sponging miR-582-5p and may serve as a therapeutic target for MM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • HMGB2 Protein / genetics
  • HMGB2 Protein / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Multiple Myeloma* / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Transcription Factors / genetics

Substances

  • HMGB2 Protein
  • MIRN582 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors
  • Proto-Oncogene Proteins c-akt