Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road No 150, Harbin 150040, China.
Department of hepatopancreatobiliary surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150040, China.
Int J Biol Sci. 2022 Jan 1;18(1):124-139. doi: 10.7150/ijbs.63598. eCollection 2022.
RNA-binding motif protein 10 (RBM10), one of the members of the RNA-binding protein (RBP) family, has a tumor suppressor role in multiple cancers. However, the functional role of RBM10 in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we observed that RBM10 is significantly downregulated in LUAD tissues compared with normal tissues. Low RBM10 expression is significantly associated with poor outcome of LUAD patients. and experiments show that RBM10 inhibits cell proliferation, metastasis and EMT progression in LUAD. Mechanistically, we demonstrate that RBM10 interacts with β-catenin interacting protein 1 (CTNNBIP1) and positively regulates its expression, disrupting the binding of β-catenin to the transcription factor TCF/LEF, thereby inactivating the Wnt/β-catenin pathway. In conclusion, this is the first study reporting the role of RBM10 in suppressing LUAD progression at least via partly inactivating the Wnt/β-catenin pathway, which provides new insights into the tumorigenesis and metastasis of LUAD. Thus, RBM10 may be a promising new therapeutic target or clinical biomarker for LUAD therapy in the future.
RNA 结合基序蛋白 10（RBM10）是 RNA 结合蛋白（RBP）家族的成员之一，在多种癌症中具有肿瘤抑制作用。然而，RBM10 在肺腺癌（LUAD）中的功能作用及其潜在的分子机制尚不清楚。在本研究中，我们观察到 RBM10 在 LUAD 组织中的表达明显低于正常组织。低 RBM10 表达与 LUAD 患者的不良预后显著相关。和实验表明，RBM10 抑制 LUAD 中的细胞增殖、转移和 EMT 进展。在机制上，我们证明 RBM10 与 β-连环蛋白相互作用蛋白 1（CTNNBIP1）相互作用，正向调节其表达，破坏 β-连环蛋白与转录因子 TCF/LEF 的结合，从而使 Wnt/β-连环蛋白通路失活。总之，这是第一项报道 RBM10 通过部分使 Wnt/β-连环蛋白通路失活来抑制 LUAD 进展的作用的研究，为 LUAD 的发生和转移提供了新的见解。因此，RBM10 可能成为未来 LUAD 治疗有前途的新的治疗靶点或临床生物标志物。
