Knockdown of BRCC3 exerts an anti‑tumor effect on cervical cancer in vitro

Mol Med Rep. 2018 Dec;18(6):4886-4894. doi: 10.3892/mmr.2018.9511. Epub 2018 Sep 26.

Abstract

Cervical cancer is a serious malignancy that affects the health of females. In the present study, the association between breast cancer type 1 susceptibility protein/breast cancer type 2 susceptibility protein‑containing complex subunit 3 (BRCC3) and cervical cancer was investigated. Reverse transcription‑quantitative polymerase chain reaction and western blotting were performed to determine BRCC3 mRNA and protein expression levels in cervical cancer tissues and cells, in addition to the expression levels of proteins associated with the epithelial‑mesenchymal transition (EMT) process in HeLa and SiHa cells. Cell Counting Kit‑8, Transwell and wound healing assays were performed to determine the cell viability, invasion and migration abilities of cervical cancer cells, respectively. The results of the present study revealed that BRCC3 expression was significantly increased in cervical cancer tissues, which was also revealed to be associated with the clinical stages and pathological grades of cervical cancer exhibited by patients, in addition to the survival time. Furthermore, BRCC3 expression levels were enhanced in HeLa, SiHa and C‑33A cervical cancer cells. BRCC3 interference in HeLa and SiHa cells was revealed to suppress cell viability, invasion and migration abilities via upregulation of E‑cadherin expression levels and downregulation of Vimentin, matrix metalloproteinase (MMP)‑2, MMP‑9, snail family transcriptional repressor (Snai)1 and Snai2 expression levels. In conclusion, the expression levels of BRCC3 were revealed to be increased in cervical cancer tissues, which were positively associated with clinical features of cervical cancer. Furthermore, BRCC3 interference inhibited the cell viability, invasion and migration abilities of HeLa and SiHa cells via regulation of EMT progression and expression levels of Snai family members. In addition, the results of the present study suggested that BRCC3 represents an oncogene associated with cervical cancer, and may also represent a novel therapeutic biomarker for the diagnosis, treatment and prognosis of patients with cervical cancer.

Keywords: breast cancer type 1 susceptibility protein/breastcancer type 2 susceptibility protein -containing complex subunit 3; cell invasion; migration; cervical cancer; snail family transcriptional repressor; epithelial-mesenchymal transition.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Survival / genetics
  • Deubiquitinating Enzymes
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Membrane Proteins / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • RNA, Messenger / genetics
  • RNA, Small Interfering
  • Snail Family Transcription Factors / metabolism
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Membrane Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Snail Family Transcription Factors
  • BRCC3 protein, human
  • Deubiquitinating Enzymes