剪接因子 RBM4 控制细胞凋亡、增殖和迁移，从而抑制肿瘤进展。
The splicing factor RBM4 controls apoptosis, proliferation, and migration to suppress tumor progression.
机构信息
Institute of Cancer Stem Cell, Second Affiliated Hospital, Cancer Center, Dalian Medical University, Dalian 116044, China; Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Pathology, First Affiliated Hospital. Dalian Medical University, Dalian 116001, China.
出版信息
Cancer Cell. 2014 Sep 8;26(3):374-389. doi: 10.1016/j.ccr.2014.07.010.
Splicing dysregulation is one of the molecular hallmarks of cancer. However, the underlying molecular mechanisms remain poorly defined. Here we report that the splicing factor RBM4 suppresses proliferation and migration of various cancer cells by specifically controlling cancer-related splicing. Particularly, RBM4 regulates Bcl-x splicing to induce apoptosis, and coexpression of Bcl-xL partially reverses the RBM4-mediated tumor suppression. Moreover, RBM4 antagonizes an oncogenic splicing factor, SRSF1, to inhibit mTOR activation. Strikingly, RBM4 expression is decreased dramatically in cancer patients, and the RBM4 level correlates positively with improved survival. In addition to providing mechanistic insights of cancer-related splicing dysregulation, this study establishes RBM4 as a tumor suppressor with therapeutic potential and clinical values as a prognostic factor.
剪接失调是癌症的分子特征之一。然而，其潜在的分子机制仍未被明确界定。在这里，我们报告了剪接因子 RBM4 通过特异性调控与癌症相关的剪接来抑制各种癌细胞的增殖和迁移。特别地，RBM4 调控 Bcl-x 的剪接以诱导细胞凋亡，并且 Bcl-xL 的共表达部分逆转了 RBM4 介导的肿瘤抑制。此外，RBM4 拮抗致癌剪接因子 SRSF1 来抑制 mTOR 的激活。引人注目的是，癌症患者中 RBM4 的表达显著降低，并且 RBM4 水平与改善的生存呈正相关。除了提供癌症相关剪接失调的机制见解外，本研究还将 RBM4 确立为一种具有治疗潜力和临床价值的肿瘤抑制因子，可作为预后因素。
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