PMID- 31322234
OWN - NLM
STAT- MEDLINE
DCOM- 20200124
LR  - 20231213
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 42
IP  - 3
DP  - 2019 Sep
TI  - Inhibition of ubiquitin‑specific protease 14 promotes connexin 32 internalization 
      and counteracts cisplatin cytotoxicity in human ovarian cancer cells.
PG  - 1237-1247
LID - 10.3892/or.2019.7232 [doi]
AB  - Although cisplatin is one of the most accepted therapies for ovarian cancer, 
      recurrence and drug resistance remain problematic. Both the ubiquitin‑proteasome 
      system (UPS) and connexin (Cx) are closely related to tumor progression. However, 
      the role of ubiquitin‑specific protease 14 (USP14) and Cx in mediating drug 
      resistance remains unclear. In the present study, we aimed to determine whether 
      USP14 is involved in cisplatin resistance and modulates the internalization of 
      connexin 32 (Cx32) in ovarian cancer. The results of the deubiquitinase (DUB) 
      trap assay and western blot analysis revealed that the expression and activity 
      levels of USP14 were downregulated in A2780 cisplatin‑resistant cells 
      (A2780‑CDDP) relative to these levels in A2780 cisplatin‑sensitive cells (A2780). 
      CCK‑8 assay results showed that inhibition of USP14 by a specific inhibitor or 
      siRNA decreased cisplatin cytotoxicity in A2780 cells. Additionally, USP14 
      inhibition increased the expression of Cx32 without changing its mRNA and 
      ubiquitination levels, as showed by Real‑time qPCR and immunoprecipitation assay 
      respectively. Cisplatin resistance induced by USP14 inhibition was counteracted 
      by Cx32 knockdown. Moreover, USP14 inhibition contributed to Cx32 
      internalization, as determined by western blot analysis and a reduction in gap 
      junction intercellular communication (GJIC), as showed by parachute dye‑coupling 
      assay. Collectively, these data suggest that Cx32 internalization by USP14 
      inhibition modulates the cisplatin resistance in ovarian cancer cells, thus 
      serving as a potential drug target to challenge chemotherapy failure. In 
      addition, USP14 can also be used as a marker to monitor the development of 
      cisplatin resistance in ovarian cancer treatment.
FAU - Luo, Huimin
AU  - Luo H
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Wang, Xiyan
AU  - Wang X
AD  - Tumor Research Institute, Xinjiang Medical University Affiliated Tumor Hospital 
      and State Key Laboratory Jointly Established by The Province and Ministry, 
      Urumqi, Xinjiang Uygur Autonomous Region 830000, P.R. China.
FAU - Ge, Hui
AU  - Ge H
AD  - Tumor Research Institute, Xinjiang Medical University Affiliated Tumor Hospital 
      and State Key Laboratory Jointly Established by The Province and Ministry, 
      Urumqi, Xinjiang Uygur Autonomous Region 830000, P.R. China.
FAU - Zheng, Ningze
AU  - Zheng N
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Peng, Fuhua
AU  - Peng F
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Fu, Yile
AU  - Fu Y
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Tao, Liang
AU  - Tao L
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Wang, Qin
AU  - Wang Q
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190715
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Connexins)
RN  - 0 (USP14 protein, human)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Cell Communication
MH  - Cell Proliferation/drug effects
MH  - Cisplatin/*pharmacology
MH  - Connexins/genetics/*metabolism
MH  - *Drug Resistance, Neoplasm
MH  - Endocytosis/*drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Ovarian Neoplasms/drug therapy/metabolism/*pathology
MH  - Tumor Cells, Cultured
MH  - Ubiquitin Thiolesterase/genetics/*metabolism
MH  - Gap Junction beta-1 Protein
EDAT- 2019/07/20 06:00
MHDA- 2020/01/25 06:00
CRDT- 2019/07/20 06:00
PHST- 2019/03/10 00:00 [received]
PHST- 2019/07/03 00:00 [accepted]
PHST- 2019/07/20 06:00 [pubmed]
PHST- 2020/01/25 06:00 [medline]
PHST- 2019/07/20 06:00 [entrez]
AID - 10.3892/or.2019.7232 [doi]
PST - ppublish
SO  - Oncol Rep. 2019 Sep;42(3):1237-1247. doi: 10.3892/or.2019.7232. Epub 2019 Jul 15.