Knockdown of PYCR1 suppressed the malignant phenotype of human hepatocellular carcinoma cells via inhibiting the AKT pathway activation

Reprod Biol. 2021 Sep;21(3):100534. doi: 10.1016/j.repbio.2021.100534. Epub 2021 Jul 13.

Abstract

Hepatocellular carcinoma (HCC) is a common and highly malignancy tumor. Pyrroline-5-carpoxylate reductase-1 (PYCR1) is an active enzyme involved in cell metabolism. In this study, we explored the role of PYCR1 in the HCC cell lines, Hep3B and HepG2. The expression of PYCR1 was up-regulated in liver hepatocellular carcinoma (LIHC) tissue by GEPIA. Meanwhile the overall survival rate (OS) showed that patients with high PYCR1 expression had a worse prognosis compared with patients with low PYCR1 level. In addition, knockdown of PYCR1 suppressed the proliferation, invasion and migration of Hep3B and HepG2 cells and promoted the apoptosis and G1 arrest. Knockdown of PYCR1 reduced the expression of the anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bax and Caspase3. Furthermore, knockdown of PYCR1 changed the expression of p-AKT and its target gene Cyclin D1. In conclusion, knockdown of PYCR1 inhibited the malignant phenotype of human HCC cells by regulating the AKT pathway activation, which provides a potential strategy for the human HCC therapy.

Keywords: AKT pathway; Apoptosis; Hepatocellular carcinoma; PYCR1; Proliferation.

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pyrroline Carboxylate Reductases / genetics
  • Pyrroline Carboxylate Reductases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcriptome
  • delta-1-Pyrroline-5-Carboxylate Reductase

Substances

  • RNA, Messenger
  • Pyrroline Carboxylate Reductases
  • Proto-Oncogene Proteins c-akt