Metastasis-associated gene 1 (MTA1) enhances cisplatin resistance of malignant pleural mesothelioma by ATR-Chk1-mediated DNA repair.

BACKGROUND

Malignant pleural mesothelioma (MPM) chemoresistance remains a challenge to oncologists. In our previous study, we demonstrated that the aberrant expression of metastasis-associated gene 1 () is associated with carcinogenesis and metastasis in MPM. The aim of the present study was to investigate the mechanism of and chemo-resistance in MPM.

METHODS

Western blotting and real-time polymerase chain reaction were used to analyze the protein and mRNA levels. A stable clone with a knockdown of was generated with shRNA via lentivirus technology in MPM cell lines. Cell Counting Kit-8 assay and crystal violet assay were used to measure cell viability. Immunochemical staining was employed to detect expression in MPM tissues. The cell cycle of MPM cells was determined by phosphohistone H3 staining and flow cytometric analysis.

RESULTS

The protein was upregulated and enhanced cisplatin resistance in MPM. Cisplatin stabilized the expression of the protein by inhibiting its ubiquitination, and enhanced G2/M cell cycle delay and regulated and protected the tumor genome from chemotherapeutic drugs via participating in the phosphorylation of the ataxia telangiectasia mutated and rad3 related-checkpoint kinase 1 () pathway.

CONCLUSIONS

These data suggest that enhances cisplatin resistance by -mediated DNA damage repairment and cisplatin stabilizes expression via affecting on the ubiquitination pathway of in MPM. Our findings indicate that could serve as a novel therapeutic target to overcome chemoresistance in MPM.