Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China.
Department of Oncology and Hematology, The Second Hospital of Jilin University, Changchun, Jilin, China.
J Cell Mol Med. 2019 Jun;23(6):3897-3904. doi: 10.1111/jcmm.14263. Epub 2019 Apr 6.
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.
初步功能研究表明，RNA 结合基序蛋白 10（RBM10）可促进细胞凋亡并抑制细胞增殖；然而，几项研究的结果表明 RBM10 具有促进肿瘤的作用。在此，我们评估了 RBM10 参与肺腺癌细胞增殖的情况，并探讨了其潜在的分子机制。我们发现，无论是在体外还是体内，RBM10 的过表达均抑制肺腺癌细胞的增殖，而敲低 RBM10 则增强细胞增殖。通过 cDNA 微阵列分析，我们先前发现 RBM10 过表达可显著下调 RAP1A 的表达。在本研究中，我们已证实 RBM10 降低了 RAP1 的激活，并且发现 EPAC 的刺激和抑制可分别消除 RBM10 敲低和过表达的作用，并调节细胞生长。RBM10 对增殖的这种影响独立于 MAPK/ERK 和 P38/MAPK 信号通路。我们发现 RBM10 通过 AKT 信号通路降低了 CREB 的磷酸化，表明 RBM10 通过 RAP1/AKT/CREB 信号通路发挥其对肺腺癌细胞增殖的作用。
