SNAP23 suppresses cervical cancer progression via modulating the cell cycle

Gene. 2018 Oct 5:673:217-224. doi: 10.1016/j.gene.2018.06.028. Epub 2018 Jun 23.

Abstract

Objective: Cervical cancer (CC) is one of the most common gynecologic tumors in women worldwide, with poor prognosis and low survival rate. In this study, we identified SNAP23 as a potential tumor suppressor gene in CC.

Methods: The expression of SNAP23 in tissues and cell lines were measured by qRT-PCR, western blot and IHC. Knockdown of SNAP23 by siRNA and ectopic expression of SNAP23 by overexpression plasmid were performed to observe the biological function of SNAP23 in CC. Xenograft nude mice models were established to measure its function in vivo.

Results: SNAP23 was downregulated in CC tissues and had a negative correlation with advanced clinical characteristics. Ectopic expression of SNAP23 suppressed malignant phonotype of CC while knockdown of SNAP23 promoted the progression of CC in vitro. The flow cytometry analysis revealed that SNAP23 exerted its tumor suppressor activity via inducing G2/M cell cycle arrest. Moreover, xenograft tumor models showed that SNAP23 suppresses tumor growth in vivo.

Conclusions: Our results revealed that SNAP23 suppressed progression of CC and induced cell cycle G2/M arrest via upregulating p21cip1 and downregulating CyclinB1.

Keywords: Cervical cancer; CyclinB1; SNAP23; p21(cip1).

MeSH terms

  • Animals
  • Cell Cycle*
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Computational Biology
  • Cyclin B1 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Disease Progression
  • Female
  • G2 Phase
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Phenotype
  • Qb-SNARE Proteins / genetics*
  • Qb-SNARE Proteins / metabolism
  • Qc-SNARE Proteins / genetics*
  • Qc-SNARE Proteins / metabolism
  • RNA, Small Interfering / metabolism
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism

Substances

  • CCNB1 protein, human
  • CDKN1A protein, human
  • Cyclin B1
  • Cyclin-Dependent Kinase Inhibitor p21
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • RNA, Small Interfering
  • SNAP23 protein, human
  • Snap23 protein, mouse