Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, the Wujin Clinical College of Xuzhou Medical University, Changzhou, China.
Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10526-10534. doi: 10.26355/eurrev_202010_23405.
Long non-coding RNAs (lncRNAs) play vital roles in the pathogenesis and development of multiple cancers, including colorectal cancer (CRC). Nevertheless, the regulatory mechanisms of LINC01278 in CRC remain unknown. Our research aims to identify the regulatory mechanisms of LINC01278 in CRC.
The expression of LINC01278 was examined by quantitative real-time polymerase chain reaction (RT-qPCR). StarBase and TargetScan websites were used to predict the interaction between miR-134 and LINC01278 or KDM2A, which was further confirmed by Dual-Luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell viability, migration, and invasion were detected by Cell Counting Kit-8 (CCK-8) and transwell assays.
LINC01278 was upregulated in CRC tissues and cell lines, and knockdown of LINC01278 suppressed CRC cell progression. In addition, LINC01278 inhibited miR-134 expression by direct interaction, and the inhibition of miR-134 abolished the suppressive effects of LINC01278 knockdown on viability, migration, and invasion of CRC cells. Furthermore, KDM2A was confirmed to be a target gene of miR-134. Overexpression of KDM2A facilitated the tumorigenesis of CRC, while this effect was reversed by the upregulation of miR-143. Finally, it was demonstrated that miR-134 inhibitor reversed the shLINC01278‑mediated inhibitory effect on KDM2A expression.
Our study demonstrated that LINC01278 upregulated KDM2A to promote CRC progression by interacting with miR-143, suggesting that LINC01278 might be a new therapeutic target of CRC.
长链非编码 RNA（lncRNA）在多种癌症的发病机制和发展中发挥着重要作用，包括结直肠癌（CRC）。然而，LINC01278 在 CRC 中的调控机制尚不清楚。我们的研究旨在确定 LINC01278 在 CRC 中的调控机制。
通过实时定量聚合酶链反应（RT-qPCR）检测 LINC01278 的表达。使用 StarBase 和 TargetScan 网站预测 miR-134 与 LINC01278 或 KDM2A 之间的相互作用，进一步通过双荧光素酶报告基因检测和 RNA 免疫沉淀（RIP）实验验证。通过细胞计数试剂盒-8（CCK-8）和 Transwell 实验检测细胞活力、迁移和侵袭。
LINC01278 在 CRC 组织和细胞系中上调，敲低 LINC01278 抑制 CRC 细胞的进展。此外，LINC01278 通过直接相互作用抑制 miR-134 的表达，而 miR-134 的抑制消除了 LINC01278 敲低对 CRC 细胞活力、迁移和侵袭的抑制作用。此外，KDM2A 被证实是 miR-134 的靶基因。过表达 KDM2A 促进 CRC 的发生，而 miR-143 的上调则逆转了这一效应。最后，研究表明 miR-134 抑制剂逆转了 shLINC01278 对 KDM2A 表达的抑制作用。
本研究表明，LINC01278 通过与 miR-143 相互作用上调 KDM2A 促进 CRC 进展，提示 LINC01278 可能成为 CRC 的新治疗靶点。
