Department of Radiation Oncology, Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, Liaoning province, China.
Department of Radiation Oncology, Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, Liaoning province, China; Department of Radiation Oncology, General Hospital of the Northern War Zone of the Chinese People's Liberation Army, Shenyang, 110016, Liaoning province, China.
Exp Cell Res. 2020 Apr 15;389(2):111884. doi: 10.1016/j.yexcr.2020.111884. Epub 2020 Feb 1.
RALY is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP), an RNA-binding protein that plays a role in mRNA splicing and metabolism, may be involved in tumorigenesis and development. Some studies have shown that RALY plays a role in promoting cancer in a variety of tumors. However, the biological function and molecular mechanism of RALY in non-small cell lung cancer (NSCLC) remain unknown. TCGA databases were used to gather RALY expression data in NSCLC, the results indicate that RALY is highly expressed in cancer tissue of NSCLC patients. Then we demonstrated that RALY gene expression was notably upregulated in NSCLC tissue and cell lines (A549 and SK-MES-1), and was associated with lymph node metastasis (P = 0.007) and poorer overall survival in NSCLC patients. Subsequently, RALY in A549 and SK-MES-1 cells was knocked down by lentivirus to analyze the consequences of RALY on the biological behavior of NSCLC cell lines. Our results indicated that RALY knockdown impaired NSCLC cells proliferation, migration, and invasion, as well as arrested cells in G1 phase, and the reintroduction of RALY recused its biological phenotype. Furthermore, RALY knockdown down-regulated the expression levels of c-Myc, Cyclin D1, CDK4, MMP9, Rho A ,Rho C, N-cadherin and β-catenin, and up-regulated the expression levels of P27, Rho B and E-cadherin. Therefore, targeting RALY could be a promising molecular target for NSCLC treatment.
RALY 是异质核核糖核蛋白（hnRNP）的成员，hnRNP 是一种 RNA 结合蛋白，在 mRNA 剪接和代谢中发挥作用，可能参与肿瘤的发生和发展。一些研究表明，RALY 在多种肿瘤中发挥促进癌症的作用。然而，RALY 在非小细胞肺癌（NSCLC）中的生物学功能和分子机制尚不清楚。TCGA 数据库用于收集 NSCLC 中 RALY 的表达数据，结果表明 RALY 在 NSCLC 患者的癌组织中高表达。然后，我们证明 RALY 基因在 NSCLC 组织和细胞系（A549 和 SK-MES-1）中表达明显上调，与淋巴结转移（P=0.007）和 NSCLC 患者的总生存率降低相关。随后，通过慢病毒敲低 A549 和 SK-MES-1 细胞中的 RALY，分析 RALY 对 NSCLC 细胞系生物学行为的影响。我们的结果表明，RALY 敲低削弱了 NSCLC 细胞的增殖、迁移和侵袭能力，使细胞停滞在 G1 期，而 RALY 的重新引入挽救了其生物学表型。此外，RALY 敲低下调了 c-Myc、Cyclin D1、CDK4、MMP9、RhoA、RhoC、N-钙黏蛋白和β-连环蛋白的表达水平，并上调了 P27、RhoB 和 E-钙黏蛋白的表达水平。因此，靶向 RALY 可能是治疗 NSCLC 的有前途的分子靶点。
