Downregulation of pyrroline-5-carboxylate reductase-2 induces the autophagy of melanoma cells via AMPK/mTOR pathway

Tumour Biol. 2016 May;37(5):6485-91. doi: 10.1007/s13277-015-3927-8. Epub 2015 Dec 3.

Abstract

Melanoma is the most aggressive form of skin cancer and causes 50,000 deaths annually worldwide. The roles of proline-dependent process and autophagy have both been reported in studies on melanoma. In the present study, we focused on the effect of pyrroline-5-carboxylate reductase-2 (PYCR2) on inducing autophagy process in melanoma. The expression of PYCR2 was regulated by an RNAi technique, and the cell proliferation of A375 cell line was determined by methyl thiazolyl tetrazolium test; the effect of PYCR2 on the apoptosis process and AMPK/mTOR pathway was evaluated by flow cytometry assay and Western blot. It was found that silence of PYCR2 resulted in the decrease of proliferative ability and activation of AMPK/mTOR-induced autophagy of A375 cells. PYCR2 silencing also activated AMPK/mTOR pathway in another melanoma cell line, CHL-1. However, the overexpression of PYCR2 seemed to make no difference to the cell viability and targeted pathway. Our results offered a preliminary illustration on the mechanism of the PYCR2-dependent autophagy and showed that PYCR2 was a potential therapeutic target of melanoma.

Keywords: AMPK/mTOR; Autophagy; Melanoma; Pyrroline-5-carboxylate reductase-2.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Apoptosis / genetics
  • Autophagy / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism*
  • Pyrroline Carboxylate Reductases / genetics*
  • Pyrroline Carboxylate Reductases / metabolism
  • RNA Interference
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Pyrroline Carboxylate Reductases
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases