Xu Caihua, Hu Yufeng, Chen Bin, Li Dapeng, Liang Rongrui, Shen Meng, Wu Mengyao, Tao Min
Department of Oncology of the First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Cardiovascular Surgery, Wuxi No. 2 People's Hospital, Wuxi, China.
Ann Transl Med. 2021 Apr;9(8):670. doi: 10.21037/atm-21-941.
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.
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.
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.
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.
恶性胸膜间皮瘤（MPM）的化疗耐药性仍然是肿瘤学家面临的一项挑战。在我们之前的研究中，我们证明了转移相关基因1（）的异常表达与MPM的致癌作用和转移相关。本研究的目的是探讨MPM中 的机制及其化疗耐药性。
采用蛋白质免疫印迹法和实时聚合酶链反应分析蛋白质和mRNA水平。通过慢病毒技术利用短发夹RNA（shRNA）在MPM细胞系中构建了一个 敲低的稳定克隆。使用细胞计数试剂盒-8法和结晶紫法测量细胞活力。采用免疫化学染色检测MPM组织中的 表达。通过磷酸化组蛋白H3染色和流式细胞术分析确定MPM细胞的细胞周期。
MPM中 蛋白上调并增强了顺铂耐药性。顺铂通过抑制 的泛素化来稳定其表达，并且 通过参与共济失调毛细血管扩张症突变和rad3相关检查点激酶1（）途径的磷酸化，增强G2/M期细胞周期阻滞，并调节和保护肿瘤基因组免受化疗药物的影响。
这些数据表明， 通过介导的DNA损伤修复增强顺铂耐药性，而顺铂通过影响MPM中 的泛素化途径来稳定 的表达。我们的研究结果表明， 可作为克服MPM化疗耐药性的一个新的治疗靶点。
