CBX3 promotes tumor proliferation by regulating G1/S phase via p21 downregulation and associates with poor prognosis in tongue squamous cell carcinoma

Gene. 2018 May 15:654:49-56. doi: 10.1016/j.gene.2018.02.043. Epub 2018 Feb 17.

Abstract

Chromobox protein homolog 3 (CBX3), a core component of the heterochromatin proteins 1, is recently proved to be involved in human cancerogenesis and associated with the prognosis of patient. However, the role of CBX3 in Tongue squamous cell carcinoma (TSCC) remains unclear. In the present study we found that CBX3 was upregulated in TSCC tissues when compared to adjacent non-tumor tissues, and multivariable analysis showed that high CBX3 expression was associated with clinical stage and cervical node metastasis, which was an independent prognostic indicator of TSCC. Furthermore, Kaplan-Meier survival analysis and log-rank test showed that TSCC patients with high CBX3 expression had a poorer rate of OS compared to patients with low CBX3 expression. Moreover, knocking down CBX3 inhibited TSCC cells proliferation both in vitro and in vivo, while overexpressing CBX3 promoted TSCC cells proliferation. In addition, CBX3 depletion resulted in cell cycle delay at the G1/S phase via the p21 pathway. In summary, we identifies CBX3 as a potential novel oncogene in TSCC, which may act as a biomarker and target in the diagnosis and treatment of this killer disease.

Keywords: CBX3; Prognosis; Proliferation; TSCC; p21.

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Down-Regulation
  • Female
  • G1 Phase
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Prognosis
  • RNA, Small Interfering / metabolism
  • S Phase
  • Smoking
  • Tongue Neoplasms / diagnosis
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • CBX3 protein, human
  • CDKN1A protein, human
  • Chromosomal Proteins, Non-Histone
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Small Interfering