WIPI1 promotes osteosarcoma cell proliferation by inhibiting CDKN1A

Gene. 2021 May 25:782:145537. doi: 10.1016/j.gene.2021.145537. Epub 2021 Feb 23.

Abstract

Detection of TCGA data revealed that WIPI1 is highly expressed in osteosarcoma cells. So we explore the mechanisms of WIPI1 affecting the proliferation of osteosarcoma cells through Affymetrix microarray analysis. Functional analysis of differentially expressed genes shows that the classical signaling pathways affecting tumor formation and development have changed significantly. By fitting analysis, it is speculated that the WIPI1 may function in the direction of osteosarcoma by regulating the expression of multiple cell cycle-related genes such as CDKN1A, CDK4 and CCND1. Therefore, the key genes are selected for RT-PCR and Western-blot verification. Combined with flow and other means, WIPI1 may affect the cell cycle and the osteosarcoma by regulating the expression of CDKN1A, CDK4 and CCND1. To verify the results, the effect of WIPI1 on cell proliferation was quantified by MTT, cell counts and nude mouse tumorigenicity assay. The results showed that WIPI1 promotes osteosarcoma cell proliferation.

Keywords: CDKN1A; Cell cycle; Cell proliferation; Osteosarcoma; WIPI1.

MeSH terms

  • Animals
  • Autophagy-Related Proteins / genetics*
  • Autophagy-Related Proteins / physiology
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Proliferation / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Gene Expression Regulation, Neoplastic
  • Genetic Vectors
  • HEK293 Cells
  • Humans
  • Lentivirus / genetics
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology
  • Mice
  • Mice, Nude
  • Oligonucleotide Array Sequence Analysis
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • Software
  • Transcriptome

Substances

  • Autophagy-Related Proteins
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Membrane Proteins
  • WIPI1 protein, human