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KIAA0101 and UbcH10 interact to regulate non-small cell lung cancer cell proliferation by disrupting the function of
Han Lei1, Kun Wang1,2, Tongying Jiang1
1Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Pudong, Shanghai, 200120, P.R. China.
Background:
Chromosome 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.
Methods:
NSCLC 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.
Results:
In 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.
Conclusions:
KIAA0101 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.
Insights
Spindle assembly checkpoint (SAC) dysfunction in non-small cell lung cancer (NSCLC) involves KIAA0101 and UbcH10 proteins. Targeting these proteins inhibits tumor growth, offering potential new NSCLC therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Spindle assembly checkpoint (SAC) dysfunction is a key driver of cancer, particularly non-small cell lung cancer (NSCLC).
- UbcH10 and KIAA0101 are implicated in SAC function and NSCLC progression.
- KIAA0101's PCNA-binding motif suggests a role in DNA repair and potential interaction with UbcH10 in regulating SAC.
Purpose of the Study:
- To investigate the interaction between KIAA0101 and UbcH10 in non-small cell lung cancer (NSCLC).
- To elucidate the role of KIAA0101 and UbcH10 in mediating SAC dysfunction and neoplastic transformation.
- To evaluate KIAA0101 and UbcH10 as potential therapeutic targets for NSCLC.
Main Methods:
- Analysis of spatial-temporal correlation between UbcH10 and KIAA0101 expression in NSCLC cell lines.
- Immunoprecipitation assays to determine the interaction mechanism between UbcH10 and KIAA0101.
- In vivo studies using tumor-bearing models to assess the effect of modulating UbcH10 and KIAA0101 on tumor growth.
Main Results:
- UbcH10 and KIAA0101 were found to be upregulated and spatially-temporally correlated in NSCLC.
- These proteins cooperate to promote premature degradation of SAC components, leading to SAC dysfunction and proliferation.
- Silencing UbcH10 and KIAA0101 significantly inhibited tumor growth in vivo.
Conclusions:
- KIAA0101 and UbcH10 interact to drive SAC dysfunction, chromosomal instability, and malignant proliferation in NSCLC.
- UbcH10 and KIAA0101 represent promising therapeutic targets for NSCLC treatment by restoring SAC function.