RNF138 confers cisplatin resistance in gastric cancer cells via activating Chk1 signaling pathway
| Autor: | Linfang Wang, Deqiang Han, Xizhe Zhang, Xuezhi Wang, Rong Huang, Jinhuan Ou, Changzheng Liu, Shijun Li, Xiaoqiao Chen, Lin Wang, Wei Song, Shiying Miao, Yalan Lu, Wenjie Liu, Changwu Ma |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Survival Ubiquitin-Protein Ligases Antineoplastic Agents Apoptosis 03 medical and health sciences Stomach Neoplasms Cell Line Tumor medicine Humans Viability assay Phosphorylation Cell Proliferation Pharmacology Cisplatin Dose-Response Relationship Drug Kinase Chemistry Cell Cycle Checkpoints Cell cycle Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Cell culture Drug Resistance Neoplasm Cancer cell Checkpoint Kinase 1 Cancer research Molecular Medicine Signal transduction medicine.drug Signal Transduction Research Paper |
| Zdroj: | Cancer biologytherapy. 19(12) |
| ISSN: | 1555-8576 |
| Popis: | Chemotherapy resistance represents a major issue associated with gastric cancer (GC) treatment, and arises through multiple mechanisms, including modulation of the cell-cycle check point. Several ubiquitin kinases, including RING finger protein 138 (RNF138), have been reported to mediate the G2/M phase arrest. In this study, we investigated the role of RNF138 in the development of cisplatin resistance of two GC cell lines. We show that RNF138 levels are higher in cisplatin-resistant cell lines, compared with cisplatin-sensitive cells, and RNF138 expression was elevated during drug withdrawal following the cisplatin treatment. Using gene overexpression and silencing, we analyzed the impact of altering RNF138 level on GC cell viability, apoptosis, and cell cycle phenotypes in two isogenic cisplatin-sensitive and resistant cell lines. We show that RNF138 overexpression increased GC cell viability, decreased apoptosis and delayed cell cycle progression in the cisplatin-sensitive GC cells. Conversely, RNF138 silencing produced opposite phenotypes in the cisplatin-resistant cells. Moreover, RNF138-dependent phosphorylation of Chk1 was seen in GC cells, indicating a novel connection between cisplatin-induced DNA damage and apoptosis. Collectively, these data suggest that RNF138 modulates the cisplatin resistance in the GC cells, thus serving as a potential drug target to challenge chemotherapy failure. In addition, RNF138 can also be used as a marker to monitor the development of cisplatin resistance in GC treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|