Liu Xiaohui, Huang Xiuzhu, Ma Jie, Li Lu, Hu Huifan, Feng Junxia, Gao Xuejuan, Zhang Yunfang, Liu Langxia
Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, Jinan University Guangzhou 510632, China.
Center of Kidney Disease, Huadu District People's Hospital, Southern Medical University Guangzhou 510800, Guangdong, China.
Am J Cancer Res. 2021 Aug 15;11(8):3857-3876. eCollection 2021.
RNA-based therapeutics has attracted substantial interest from both academics and pharmaceutical companies. In this study, we investigated the function and the underlying mechanism of 3'UTR in NSCLC H1299 and A549 cells. We found that transfected plasmids significantly increased the proliferation, migration and invasion of NSCLC cells, whereas 3'UTR could suppress the promotional effect of GSN protein on the development of NSCLC . Interestingly, we observed that these anticancer effects of 3'UTR was independent of the co-expression with GSN coding sequence. Moreover, transfected 3'UTR affected the actin-cytoskeleton remodeling and epithelial-mesenchymal transition (EMT) processes in H1299 and A549 cells, and targeted the co-expressed proteins to the plasma membrane. Subsequently, RNA pull-down assays have been performed to identify Tra2β protein as a 3'UTR binder. We then showed that Tra2β was important for the localized protein expression mediated by 3'UTR. Taken together, our results suggested that 3'UTR may exert anticancer functions in NSCLC cells through regulating the subcellular localized expression of GSN protein mediated by the interaction between 3'UTR-Tra2β.
基于RNA的疗法已引起学术界和制药公司的广泛关注。在本研究中,我们研究了3'UTR在非小细胞肺癌H1299和A549细胞中的功能及潜在机制。我们发现转染质粒显著增加了非小细胞肺癌细胞的增殖、迁移和侵袭,而3'UTR可抑制GSN蛋白对非小细胞肺癌发展的促进作用。有趣的是,我们观察到3'UTR的这些抗癌作用与GSN编码序列的共表达无关。此外,转染的3'UTR影响H1299和A549细胞中的肌动蛋白细胞骨架重塑和上皮-间质转化(EMT)过程,并将共表达蛋白靶向至质膜。随后,进行了RNA下拉实验以鉴定Tra2β蛋白为3'UTR结合蛋白。然后我们表明Tra2β对于3'UTR介导的局部蛋白表达很重要。综上所述,我们的结果表明3'UTR可能通过调节由3'UTR-Tra2β相互作用介导的GSN蛋白亚细胞定位表达,在非小细胞肺癌细胞中发挥抗癌功能。