Department of Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang, Liaoning, China.
Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang, Liaoning, China.
J Cell Physiol. 2020 Feb;235(2):1453-1468. doi: 10.1002/jcp.29065. Epub 2019 Jul 5.
Our study was intended to provide evidence for whether long noncoding RNA (lncRNA) SNHG1 would accelerate the epithelial-mesenchymal transition (EMT) course intrinsic in colorectal cancer (CRC) by sponging downstream miR-497-5p and miR-195-5p. We altogether collected 338 pairs of CRC and noncancerous tissues, and meanwhile purchased five CRC cell lines (i.e., SW480, HCT116, Lovo, CaCO-2, and HT29) and human embryo intestinal mucosal tissue-sourced cell line (i.e., CCC-HIE-2). The CRC cells as mentioned above were appraised regarding their potencies in proliferation, migration, and invasion, after being transfected with pcDNA3.1-SNHG1, si-SNHG1, miR-195-5p mimic/inhibitor, and miR-497-5p mimic/inhibitor. Eventually, we depended on reverse transcription-polymerase chain reaction to assess SNHG1, miR-497-5p, and miR-195-5p expressions, and the protein levels of EMT-specific molecules were determined on the strength of western blotting. It seemed that there was a high potential for highly expressed SNHG1 and lowly expressed miR-497/miR-195 to symbolize CRC patients' unfavorable prognosis (p < .05). Concurrently, CRC cells were detected with higher SNHG1 expression and lower miR-497/miR-195 expression than CCC-HIE-2 cells (p < .05). In addition, the EMT process of CRC cells was facilitated markedly against the contexts of overexpressed SNHG1 and underexpressed miR-497-5p/miR-195-5p. Intriguingly, the strength of miR-195-5p collaborating with miR-497-5p in affecting the activity of CRC cells seemed to overweigh that of miR-497/miR-195-5p alone. Besides, both miR-195-5p and miR-497-5p were subjected to in vivo and in vitro modification of SNHG1 (p < .05). Conclusively, application of lncRNA SNHG1 for treating CRC might be promising, given its dual modulation of miR-497 and miR-195 underlying CRC pathogenesis.
我们的研究旨在提供证据，证明长链非编码 RNA (lncRNA) SNHG1 是否通过海绵吸附下游 miR-497-5p 和 miR-195-5p 来加速结直肠癌 (CRC) 内在的上皮-间充质转化 (EMT) 过程。我们总共收集了 338 对 CRC 和非癌组织，同时购买了 5 种 CRC 细胞系（即 SW480、HCT116、Lovo、CaCO-2 和 HT29）和人胚胎肠黏膜组织来源的细胞系（即 CCC-HIE-2）。上述 CRC 细胞在转染 pcDNA3.1-SNHG1、si-SNHG1、miR-195-5p 模拟物/抑制剂和 miR-497-5p 模拟物/抑制剂后，评估其增殖、迁移和侵袭能力。最终，我们依赖逆转录-聚合酶链反应来评估 SNHG1、miR-497-5p 和 miR-195-5p 的表达，并通过 Western blot 确定 EMT 特异性分子的蛋白水平。似乎高表达的 SNHG1 和低表达的 miR-497/miR-195 有很高的可能性预示着 CRC 患者的不良预后（p <.05）。同时，CRC 细胞的 SNHG1 表达高于 CCC-HIE-2 细胞，miR-497/miR-195 表达低于 CCC-HIE-2 细胞（p <.05）。此外，CRC 细胞的 EMT 过程明显促进了高表达 SNHG1 和低表达 miR-497-5p/miR-195-5p 的表达。有趣的是，miR-195-5p 与 miR-497-5p 协同作用影响 CRC 细胞活性的强度似乎超过了 miR-497/miR-195-5p 单独作用的强度。此外，miR-195-5p 和 miR-497-5p 都受到 SNHG1 的体内和体外修饰（p <.05）。总之，由于 lncRNA SNHG1 对 CRC 发病机制中 miR-497 和 miR-195 的双重调节作用，应用 SNHG1 治疗 CRC 可能是有前途的。
