LncRNA-MALAT1 Regulates Cancer Glucose Metabolism in Prostate Cancer via MYBL2/mTOR Axis

Oxid Med Cell Longev. 2022 May 2:2022:8693259. doi: 10.1155/2022/8693259. eCollection 2022.

Abstract

It is known that the long noncoding RNAs (lncRNA) MALAT1 is associated with tumorigenesis and progression in various cancers; however, its functions and mechanisms in prostate cancer (PCa) initiation and progression are still unknown. In the present study, our findings revealed that MALAT1 plays a critical part in regulating PCa proliferation and glucose metabolism. Knockdown of MALAT1 affects the protein and mRNA levels of MYBL2. In addition, MALAT1 enhances the phosphorylation level of mTOR pathway by upregulating MYBL2. Knockdown of MALAT1 or MYBL2 in PCa cell lines significantly inhibits their proliferation capacity. Silencing MALAT1/MYBL2/mTOR axis in PCa cell lines affects their glycolysis and lactate levels, and we verified these findings in mice. Furthermore, we explored the underlying tumorigenesis functions of MYBL2 in PCa and found that high expression of MYBL2 was positively associated with TNM stage, Gleason score, PSA level, and poor survival rate in PCa patients. Taken together, our research suggests that MALAT1 controls cancer glucose metabolism and progression by upregulating MYBL2-mTOR axis.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Cell Cycle Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glucose* / metabolism
  • Humans
  • Male
  • Mice
  • MicroRNAs* / genetics
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • RNA, Long Noncoding* / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Trans-Activators* / metabolism

Substances

  • Cell Cycle Proteins
  • MALAT1 long non-coding RNA, human
  • MYBL2 protein, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Trans-Activators
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Glucose