KIAA0101 and UbcH10 interact to regulate non-small cell lung cancer cell proliferation by disrupting the function of the spindle assembly checkpoint

BMC Cancer

Tongying Jiang¹  Han Lei¹  Jingjing Lu¹  Feilong Wang¹  Xue Dong¹  Qiang Li¹  Liming Zhao²  Kun Wang³ 

[1] Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Pudong, 200120, Shanghai, P.R. China;Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Pudong, 200120, Shanghai, P.R. China;Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 1800 Yuntai Road, Pudong, 200120, Shanghai, P.R. China;Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Pudong, 200120, Shanghai, P.R. China;Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, 200080, Shanghai, China;

关键词: Non-small cell lung cancer;    Spindle assembly checkpoint;    UbcH10;    KIAA0101;   

DOI  :  10.1186/s12885-020-07463-3

来源: Springer

【 摘 要 】

BackgroundChromosome mis-segregation caused by spindle assembly checkpoint (SAC) dysfunction during mitosis is an important pathogenic factor in cancer, and modulating SAC function has emerged as a potential novel therapy for non-small cell lung cancer (NSCLC). UbcH10 is considered to be associated with SAC function and the pathological types and clinical grades of NSCLC. KIAA0101, which contains a highly conserved proliferating cell nuclear antigen (PCNA)-binding motif that is involved in DNA repair in cancer cells, plays an important role in the regulation of SAC function in NSCLC cells, and bioinformatics predictions showed that this regulatory role is related to UbcH10. We hypothesized KIAA0101 and UbcH10 interact to mediate SAC dysfunction and neoplastic transformation during the development of USCLC.MethodsNSCLC cell lines were used to investigate the spatial-temporal correlation between UbcH10 and KIAA0101 expression and the downstream effects of modulating their expression were evaluated. Further immunoprecipitation assays were used to investigate the possible mechanism underlying the correlation between UbcH10 and KIAA0101. Eventually, the effect of modulating UbcH10 and KIAA010 on tumor growth and its possible mechanisms were explored through in vivo tumor-bearing models.ResultsIn this study, we demonstrated that both UbcH10 and KIAA0101 were upregulated in NSCLC tissues and cells and that their expression levels were correlated in a spatial and temporal manner. Importantly, UbcH10 and KIAA0101 coordinated to mediate the premature degradation of various SAC components to cause further SAC dysfunction and neoplastic proliferation. Moreover, tumor growth in vivo was significantly inhibited by silencing UbcH10 and KIAA0101 expression.ConclusionsKIAA0101 and UbcH10 interact to cause SAC dysfunction, chromosomal instability and malignant proliferation in NSCLC, suggesting that UbcH10 and KIAA0101 are potential therapeutic targets for the treatment of NSCLC by ameliorating SAC function.

【 授权许可】

CC BY