Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
Int J Oncol. 2019 Feb;54(2):467-478. doi: 10.3892/ijo.2018.4643. Epub 2018 Nov 22.
Lung cancer is one of the most common causes of morbidity and mortality among malignant tumors worldwide. The poor prognosis of patients with lung adenocarcinomas is primarily due to its strong ability to invade and metastasize. Recent research has indicated that RNA‑binding protein 10 (RBM10) is mutated in lung adenocarcinoma, and is closely associated with tumor proliferation and apoptosis; however, the precise role of RBM10 in lung adenocarcinoma remains unclear. Our preliminary experiments (unpublished data) revealed that RBM10 expression was upregulated in lung adenocarcinoma cell lines and tissues. In this study, we first detected the protein expression level of RBM10 in lung adenocarcinoma cells and tissues, and we then examined the effects of RBM10 overexpression and downregulation (via small interfering RNA) on the proliferation and apoptosis of stable lung adenocarcinoma cells, along with its possible mechanisms of action. We also used clinical samples of lung adenocarcinomas to verify our results. We found that RBM10 protein was overexpressed in lung adenocarcinoma cells and tissues, and it reduced p53 expression (as detected by immunofluorescence assay and western blot analysis) in A549 cells and inhibited apoptosis (as shown by flow cytometric assay). RBM10 also promoted cell growth and proliferation in vitro and increased cell migration in a cell wound scratch assay. Furthermore, we found that RBM10 activated key proliferative signaling pathways [such as the epidermal growth factor receptor (EGFR), mitogen‑activated protein kinase (MAPK) and phosphoinositide 3‑kinase (PI3K)‑AKT pathways] and inhibited apoptotic pathways. In addition, we demonstrated that a high expression of RBM10 protein in patient tissue samples was associated with a shorter overall survival time and a poor prognosis. On the whole, the findings of this study indicate that RBM10 may function as an oncogene in lung cancer, and may thus prove to be a novel therapeutic target for the prophylaxis and treatment of lung adenocarcinomas.
肺癌是全球恶性肿瘤发病率和死亡率最高的疾病之一。肺腺癌患者预后不良主要是由于其侵袭和转移能力较强。最近的研究表明，RNA 结合蛋白 10（RBM10）在肺腺癌中发生突变，与肿瘤增殖和凋亡密切相关；然而，RBM10 在肺腺癌中的确切作用尚不清楚。我们的初步实验（未发表的数据）显示，RBM10 在肺腺癌细胞系和组织中表达上调。在本研究中，我们首先检测了 RBM10 在肺腺癌细胞和组织中的蛋白表达水平，然后研究了 RBM10 过表达和下调（通过小干扰 RNA）对稳定肺腺癌细胞增殖和凋亡的影响，以及其可能的作用机制。我们还使用肺腺癌的临床样本验证了我们的结果。我们发现 RBM10 蛋白在肺腺癌细胞和组织中过度表达，它降低了 A549 细胞中 p53 的表达（通过免疫荧光检测和 Western blot 分析），并抑制了细胞凋亡（通过流式细胞术检测）。RBM10 还促进了体外细胞生长和增殖，并增加了细胞划痕实验中的细胞迁移。此外，我们发现 RBM10 激活了关键的增殖信号通路（如表皮生长因子受体（EGFR）、丝裂原活化蛋白激酶（MAPK）和磷酸肌醇 3-激酶（PI3K）-AKT 通路），并抑制了凋亡通路。此外，我们证明了患者组织样本中 RBM10 蛋白的高表达与总生存时间缩短和预后不良相关。总的来说，这项研究的结果表明，RBM10 可能在肺癌中作为癌基因发挥作用，因此可能成为预防和治疗肺腺癌的新治疗靶点。
