LncRNA LINC01270 aggravates the progression of gastric cancer through modulation of miR-326/EFNA3 axis

Gastric cancer (GC) is lethal malignancy, which is associated with high mortality. Long noncoding RNA LINC01270 has been identified to act as a potential oncogene in several cancers. However, its role and related regulatory mechanism in GC are yet to be illustrated. The levels of lncRNA LINC01270, miR-326, and EphrinA3 (EFNA3) were assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) and colony formation assays were applied for analyzing cell proliferation. Transwell assay was used for measuring cellular migration and invasion. Western blot analysis was employed for evaluating the protein levels. Luciferase reporter and RNA pull-down assays were utilized to verify the binding ability between LINC01270 (or EFNA3) and miR-326. Our findings indicated that LINC01270 expression was significantly up-regulated in GC tissues and cell lines. Additionally, LINC01270 knockdown attenuated GC progression through inhibiting cell proliferation, migration, and invasion. Functional experiments identified that lncRNA LINC01270 could positively regulate EFNA3 expression by serving as a competing endogenous RNA (ceRNA) for miR-326. Through rescue assays, inhibition of GC progression caused by LINC01270 suppression was found to be reversed by the application of miR-326 inhibitor or EFNA3 overexpression. Overall, our work demonstrated that lncRNA LINC01270 can accelerate cell proliferation, migration, and invasion via modulating miR-326/EFNA3 axis. These findings might implicate the potential role of lncRNA LINC01270 in GC treatment.胃癌（GC）是致死性恶性肿瘤，死亡率居高不下。长链非编码RNA（long noncoding RNA）LINC01270已被证实可在多种癌症中充当潜在癌基因，但其在胃癌中的具体作用及相关调控机制仍有待阐明。本研究采用定量反转录聚合酶链反应（qRT-PCR）检测了lncRNA LINC01270、miR-326与EphrinA3（EFNA3）的表达水平；通过细胞计数试剂盒-8（CCK-8）实验与集落形成实验分析细胞增殖能力，利用Transwell实验检测细胞迁移与侵袭能力，采用蛋白质免疫印迹分析（Western blot）评估蛋白表达水平。研究人员借助荧光素酶报告基因实验（Luciferase reporter assay）与RNA下拉实验（RNA pull-down assay），验证了LINC01270（或EFNA3）与miR-326之间的结合能力。本研究结果显示，LINC01270在胃癌组织与细胞系中的表达量显著上调；敲低LINC01270可通过抑制细胞增殖、迁移与侵袭，延缓胃癌进程。功能实验证实，lncRNA LINC01270可作为miR-326的内源竞争RNA（ceRNA），正向调控EFNA3的表达。通过拯救实验发现，使用miR-326抑制剂或过表达EFNA3，可逆转LINC01270敲低所介导的胃癌进程抑制效应。综上，本研究证实lncRNA LINC01270可通过调控miR-326/EFNA3轴，加速胃癌细胞的增殖、迁移与侵袭能力。上述研究结果提示，lncRNA LINC01270可能在胃癌治疗中发挥潜在作用。