LINC01088/miR-22/CDC6 Axis Regulates Prostate Cancer Progression by Activating the PI3K/AKT Pathway

Mediators Inflamm. 2023 Jul 19:2023:9207148. doi: 10.1155/2023/9207148. eCollection 2023.

Abstract

Background: Prostate cancer (PCa) harms the male reproductive system, and lncRNA may play an important role in it. Here, we report that the LINC01088/microRNA- (miRNA/miR-) 22/cell division cycle 6 (CDC6) axis regulated through the phosphatidylinositide 3-kinases- (PI3K-) protein kinase B (AKT) signaling pathway controls the development of PCa.

Methods: lncRNA/miRNA/mRNA associated with PCa was downloaded and analyzed by Gene Expression Omnibus. The expression and correlation of LINC01088/miR-22/CDC6 in PCa were analyzed and verified by RT-qPCR. Dual-luciferase was used to analyze the binding between miR-22 and LINC01088 or CDC6. Cell Counting Kit-8 and Transwell were used to analyze the effects of LINC01088/miR-22/CDC6 interactions on PCa cell viability or migration/invasion ability. Localization of LINC01088 in cells was analyzed by nuclear cytoplasmic separation. The effect of LINC01088/miR-22/CDC6 interaction on downstream PI3K/AKT signaling was analyzed by Western blot.

Results: LINC01088 or CDC6 was upregulated in prostate tumor tissues or cells, whereas miR-22 was downregulated, miR-22 directly targets both LINC01088 and CDC6. si-LINC01088 inhibits the PCa process by suppressing the PI3K/AKT pathway. CDC6 reverses si-linc01088-mediated cell growth inhibition and reduction of PI3K and AKT protein levels.

Conclusion: Our results demonstrate that the LINC01088/miR-22/CDC6 axis functions in PCa progression and provide a promising diagnostic and therapeutic target.

MeSH terms

  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nuclear Proteins
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prostatic Neoplasms* / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding* / genetics

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • RNA, Long Noncoding
  • MicroRNAs
  • CDC6 protein, human
  • Nuclear Proteins
  • Cell Cycle Proteins
  • MIRN22 microRNA, human