Ye Guang-Yao, Zhang Zi-Zhen, Zhu Chun-Chao, Cong Zhi-Jie, Cui Zhe, Chen Lu, Zhao Gang
Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Oncol. 2021 Aug 6;11:727698. doi: 10.3389/fonc.2021.727698. eCollection 2021.
Long non-coding RNAs (lncRNAs) display regulatory function flexibly in tumor onset and developments. Our study aimed to delve into the roles of lncRNA LINC01569 (LINC01569) in colorectal cancer (CRC) progression to study the potential mechanisms.
The genetic expression profiles of miR-381-3p and LINC01569 were measured by RT-PCR. The subcellular localization of LINC01569 in CRC cells was identified using subcellular fractionation location. Loss-of-function assays were performed to explore the potential effects of LINC01569 on CRC progression. Dual-luciferase reporter analysis was employed to verify the binding connections among LINC01569, miR-381-3p, and RAP2A.
LINC01569 expression was distinctly increased in CRC. Curiously, if LINC01569 is removed, CRC cells will not migrate, proliferate, and invade remarkably. Molecular mechanism exploration uncovered that LINC01569 acted as a ceRNA competing with RAP2A to bind with miR-381-3p. Furthermore, rescue experiments corroborated the fact that miR-381-3p suppression reversed the inhibitory actions of LINC01569 knockdown on the expression of RAP2A and CRC progression.
Overall, our findings indicate that LINC01569 plays a key role in CRC development by means of aiming at the miR-381-3p/RAP2A axis and can be equivalent to an underlying medicinal target to save CRC patients.
长链非编码RNA（lncRNAs）在肿瘤的发生和发展中灵活地发挥调节功能。我们的研究旨在深入探讨lncRNA LINC01569（LINC01569）在结直肠癌（CRC）进展中的作用，以研究其潜在机制。
通过RT-PCR检测miR-381-3p和LINC01569的基因表达谱。利用亚细胞分级定位鉴定LINC01569在CRC细胞中的亚细胞定位。进行功能缺失实验以探索LINC01569对CRC进展的潜在影响。采用双荧光素酶报告基因分析来验证LINC01569、miR-381-3p和RAP2A之间的结合关系。
LINC01569在CRC中的表达明显增加。奇怪的是，如果去除LINC01569，CRC细胞将不会显著迁移、增殖和侵袭。分子机制探索发现，LINC01569作为一种竞争性内源RNA（ceRNA），与RAP2A竞争结合miR-381-3p。此外，挽救实验证实了miR-381-3p抑制可逆转LINC01569敲低对RAP2A表达和CRC进展的抑制作用。
总体而言，我们的研究结果表明，LINC01569通过靶向miR-381-3p/RAP2A轴在CRC发展中起关键作用，并且可以作为一种潜在的治疗靶点来拯救CRC患者。
