LOC100996425 acts as a promoter in prostate cancer by mediating hepatocyte nuclear factor 4A and the AMPK/mTOR pathway

J Cell Mol Med. 2021 Sep;25(17):8174-8186. doi: 10.1111/jcmm.16657. Epub 2021 Jul 26.

Abstract

The involvement of long non-coding RNAs (lncRNAs), differentially expressed genes and signals in prostate cancer (PCa) continues to be a subject of investigation. This study determined effects of LOC100996425 on human PCa by targeting hepatocyte nuclear factor 4A (HNF4A) via the AMPK/mTOR pathway. PCa and adjacent normal tissues were obtained to characterize expression pattern of LOC100996425, HNF4A and the AMPK/mTOR pathway-related genes. Then, the target gene of LOC100996425 was determined with lncRNA target prediction website and further verification was obtained through luciferase assay and ribonucleoprotein immunoprecipitation. After that, PCa cells were introduced with LOC100996425, HNF4A, siLOC100996425 or siHNF4A to explore the specific significance of LOC100996425 and HNF4A in PCa. The mechanism associated with AMPK/mTOR pathway was investigated using AMPK inhibitor or activator. LOC100996425 was up-regulated, while HNF4A was down-regulated in the PCa tissues. HNF4A was a target gene of LOC100996425. PCa cells transfected with either siLOC100996425 or HNF4A displayed reduced rates of PCa cell proliferation and migration while elevating cell apoptosis. HNF4A overexpression reversed the promotive effect of LOC100996425 overexpression on PCa. The activation of AMPK pathway involved in the cancer progression mediated by LOC100996425. Down-regulation of LOC100996425 retards progression of PCa through HNF4A-mediated AMPK/mTOR pathway.

Keywords: AMPK; LOC100996425; hepatocyte nuclear factor 4A; long non-coding RNA; mTOR pathway; prostate cancer.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Hepatocyte Nuclear Factor 4 / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Prostatic Neoplasms / metabolism*
  • RNA, Long Noncoding / physiology*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • LOC101926975 long non-coding RNA, human
  • RNA, Long Noncoding
  • MTOR protein, human
  • TOR Serine-Threonine Kinases