Overexpression of CKS2 is associated with a poor prognosis and promotes cell proliferation and invasion in breast cancer

Mol Med Rep. 2019 Jun;19(6):4761-4769. doi: 10.3892/mmr.2019.10134. Epub 2019 Apr 5.

Abstract

Growing evidence indicates that cyclin dependent kinases regulatory subunit 2 (CKS2) serves an essential role in the regulation of multiple cellular processes in diverse human cancer types. The present study investigated the contribution of CKS2 to breast cancer (BC) progression. In the present study, CKS2 expression in BC was detected using Oncomine and The Cancer Genome Atlas database. The association between expression levels and clinical features was explored using Kaplan‑Meier plotter and the Breast Cancer Gene‑Expression Miner Version 4.0 (bc‑GenExMiner) online database. In addition, the roles of CKS2 in BC progression were examined. It was identified that CKS2 expression was significantly increased in BC tissues at the mRNA and protein levels. Bc‑GenExMiner demonstrated that high CKS2 expression was associated with a positive estrogen receptor status, progesterone receptor status, nodal status and basal‑like status. High CKS2 expression was markedly associated with poor overall survival, relapse‑free survival, and distant metastasis‑free survival in patients with BC. Moreover, functional assays revealed that CKS2 inhibition suppressed cell proliferation and invasion ability in vitro and reduced tumor growth in vivo. Thus, the present findings suggested that CKS2 may act as a potential biomarker and therapeutic target for the treatment of BC.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • CDC2-CDC28 Kinases / genetics
  • CDC2-CDC28 Kinases / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Kaplan-Meier Estimate
  • Mice, Inbred BALB C
  • Prognosis
  • RNA, Messenger / metabolism
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Carrier Proteins
  • Cell Cycle Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, Progesterone
  • CDC2-CDC28 Kinases
  • CKS2 protein, human