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RBM10 inhibits cell proliferation of lung adenocarcinoma via RAP1/AKT/CREB signalling pathway
Xin Jin1,2, Xin Di1, Ruimin Wang3
1Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China.
Abstract:
Initial functional studies have demonstrated that RNA-binding motif protein 10 (RBM10) can promote apoptosis and suppress cell proliferation; however, the results of several studies suggest a tumour-promoting role for RBM10. Herein, we assessed the involvement of RBM10 in lung adenocarcinoma cell proliferation and explored the potential molecular mechanism. We found that, both in vitro and in vivo, RBM10 overexpression suppresses lung adenocarcinoma cell proliferation, while its knockdown enhances cell proliferation. Using complementary DNA microarray analysis, we previously found that RBM10 overexpression induces significant down-regulation of RAP1A expression. In this study, we have confirmed that RBM10 decreases the activation of RAP1 and found that EPAC stimulation and inhibition can abolish the effects of RBM10 knockdown and overexpression, respectively, and regulate cell growth. This effect of RBM10 on proliferation was independent of the MAPK/ERK and P38/MAPK signalling pathways. We found that RBM10 reduces the phosphorylation of CREB via the AKT signalling pathway, suggesting that RBM10 exhibits its effect on lung adenocarcinoma cell proliferation via the RAP1/AKT/CREB signalling pathway.
Insights
RNA-binding motif protein 10 (RBM10) suppresses lung adenocarcinoma cell proliferation by inhibiting the RAP1/AKT/CREB pathway. RBM10 knockdown enhances proliferation, revealing its complex role in cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- RNA-binding motif protein 10 (RBM10) has conflicting roles in cancer, with some studies suggesting tumor promotion.
- Understanding RBM10's precise function in lung adenocarcinoma is crucial for targeted therapies.
Purpose of the Study:
- To investigate the role of RBM10 in lung adenocarcinoma cell proliferation.
- To elucidate the molecular mechanisms underlying RBM10's effects on cancer growth.
Main Methods:
- In vitro and in vivo experiments assessing cell proliferation with RBM10 overexpression and knockdown.
- Complementary DNA microarray analysis to identify affected pathways.
- Western blotting and pathway activators/inhibitors (EPAC, AKT pathway) to confirm molecular interactions.
Main Results:
- RBM10 overexpression suppressed lung adenocarcinoma cell proliferation, while RBM10 knockdown enhanced it.
- RBM10 was found to decrease RAP1 activation and CREB phosphorylation.
- The proliferation effects were mediated through the RAP1/AKT/CREB signaling pathway, independent of MAPK/ERK and P38/MAPK.
Conclusions:
- RBM10 acts as a suppressor of lung adenocarcinoma cell proliferation.
- The RAP1/AKT/CREB pathway is a key mediator of RBM10's anti-proliferative effects in this cancer type.
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