CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration

Oncotarget. 2015 Sep 22;6(28):25856-67. doi: 10.18632/oncotarget.4624.

Abstract

The coiled coil is a superhelical structural protein motif involved in a diverse array of biological functions, and the abnormal expression of the coiled-coil domain containing proteins has a direct link with the phenotype of tumor cell migration, invasion and metastasis. The aim of this study was to investigate the critical role of Coiled-coil domain-containing protein 34 (CCDC34) in bladder carcinogenesis, which has never been reported to date. Here, we found CCDC34 expression was elevated in bladder cancer tissues and cell lines. The knockdown of CCDC34 via lentivirus-mediated siRNA significantly suppressed bladder cancer cells proliferation and migration, and induced cell cycle arrest at G2/M phase and increased apoptosis in vitro. In addition, CCDC34 knockdown suppressed bladder tumor growth in nude mice. Moreover, CCDC34 silencing decreased the phosphorylation of MEK, ERK1/2, JNK, p38 and Akt, and the expressions of c-Raf and c-Jun, indicating MAPK and AKT pathways (ERK/MAPK, p38/MAPK, JNK/MAPK and PI3K/Akt) might be involved in CCDC34 regulation of bladder cancer cell proliferation and migration. Our findings revealed for the first time a potential oncogenic role for CCDC34 in bladder carcinoma pathogenesis and it may serve as a biomarker or even a therapeutic target for bladder cancer.

Keywords: CCDC34; bladder cancer; migration; proliferation; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Enzyme Activation
  • Female
  • G2 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNAi Therapeutics
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden
  • Up-Regulation
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • Antigens, Neoplasm
  • CCDC34 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases