Department of Colorectal & Anal Surgery Shanxi Provincial People's Hospital, Taiyuan, China.
Cell Cycle. 2022 Feb;21(3):228-246. doi: 10.1080/15384101.2021.2015670. Epub 2021 Dec 29.
As a newly discovered cancer-related molecule, we explored the unreported mechanism of LINC01615 intervention in colon cancer.LINC01615 expression in clinical samples and cells were detected. Effects of LINC01615 silencing/overexpression on the malignant development of colon cancer cells were analyzed through cell function experiments. Changes at the level of molecular biology were detected by quantitative real-time polymerase chain reaction and Western blot. Bioinformatics analysis and dual luciferase reporter assay were involved in the display and verification of targeted binding sequences. The rescue tests and correlation analysis examined the relationship among LINC01615, miR-3653-3p and zinc finger E-box binding homeobox 2 (ZEB2) in colon cancer cells. The xenograft experiment and immunohistochemistry were performed to verify these results.TCGA suggested that LINC01615 was high-expressed in colon cancer, as verified in clinical and cell samples, and patients with LINC01615 overexpression suffered from a poor prognosis. Silent LINC01615 blocked the malignant development of colon cancer cells through regulating related genes expressions, while overexpressed LINC01615 had the opposite effect. LINC01615, which was targeted by miR-3653-3p, partially offset the inhibitory effect of miR-3653-3p on colon cancer cells. The downstream target gene ZEB2 of miR-3653-3p was high-expressed in colon cancer. MiR-3653-3p was negatively correlated with LINC01615 or ZEB2, while LINC01615 was positively correlated with ZEB2. Therefore, LINC01615 induced ZEB2 up-regulation, while miR-3653-3p reduced ZEB2 level. The results of studies were consistent with cell experiments.LINC01615 competitively binds with miR-3653-3p to regulate ZEB2 and promote canceration of colon cancer cells.
作为一个新发现的与癌症相关的分子，我们探索了 LINC01615 干预结肠癌的未报道机制。检测了临床样本和细胞中 LINC01615 的表达。通过细胞功能实验分析 LINC01615 沉默/过表达对结肠癌细胞恶性发展的影响。通过定量实时聚合酶链反应和 Western blot 检测分子生物学水平的变化。涉及生物信息学分析和双荧光素酶报告基因检测来显示和验证靶向结合序列。通过 rescue 测试和相关性分析来检测 LINC01615、miR-3653-3p 和锌指 E 盒结合同源盒 2（ZEB2）在结肠癌细胞中的关系。通过异种移植实验和免疫组织化学验证这些结果。TCGA 表明 LINC01615 在结肠癌中高表达，在临床和细胞样本中得到验证，LINC01615 过表达的患者预后不良。沉默 LINC01615 通过调节相关基因的表达来阻断结肠癌细胞的恶性发展，而过表达 LINC01615 则有相反的作用。LINC01615 是 miR-3653-3p 的靶向分子，部分抵消了 miR-3653-3p 对结肠癌细胞的抑制作用。miR-3653-3p 的下游靶基因 ZEB2 在结肠癌中高表达。miR-3653-3p 与 LINC01615 或 ZEB2 呈负相关，而 LINC01615 与 ZEB2 呈正相关。因此，LINC01615 诱导 ZEB2 上调，而 miR-3653-3p 降低 ZEB2 水平。研究结果与细胞实验一致。LINC01615 与 miR-3653-3p 竞争结合，调节 ZEB2，促进结肠癌细胞癌变。
