Department of Thoracic Surgery, 91631Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221089000. doi: 10.1177/09603271221089000.
LINC00511 has been reported as a biomarker related to the prognosis of non-small cell lung cancer (NSCLC), but the molecular mechanism and exact functions of LINC00511 in chemoresistance of NSCLC remain to be elucidated.
RT-qPCR was used to evaluate the mRNA expression of LINC00511, miR-625, and leucine rich repeat containing 8 volume-regulated anion channel subunit E (LRRC8E). Western blotting detected the protein levels of Ki-67, MMP-9, cleaved-caspase-3. The interaction between miR-625 and LINC00511 or LRRC8E was verified by luciferase reporter assays. CCK-8, TUNEL, and Transwell assays were used to evaluate IC value, proliferation, migration, and invasion of NSCLC cells.
In our study, it was discovered that the levels of LINC00511 and LRRC8E were increased, while miR-625 expression was decreased in NSCLC tissues, DDP-resistant NSCLC cells, and non-resistant NSCLC cells. LINC00511 depletion significantly curbed cell growth, IC value, and metastasis in DDP-resistant NSCLC cells. In addition, the influence of LINC00511 deficiency on the DDP resistance in NSCLC was overturned by suppressing miR-625. Furthermore, LRRC8E overexpression abolished the promotive effect of miR-625 abundance on the DDP sensitivity in DDP-resistant NSCLC cells.
Our results demonstrated that LINC00511 increased DDP resistance in NSCLC by suppressing miR-625 to upregulate LRRC8E.
已有研究表明 LINC00511 是与非小细胞肺癌（NSCLC）预后相关的生物标志物，但 LINC00511 在 NSCLC 化疗耐药中的分子机制和确切功能仍有待阐明。
采用 RT-qPCR 检测 LINC00511、miR-625 和富含亮氨酸重复序列的 8 个卷曲螺旋结构域受体蛋白 E（LRRC8E）的 mRNA 表达。Western blot 检测 Ki-67、MMP-9、cleaved-caspase-3 的蛋白水平。通过荧光素酶报告实验验证 miR-625 与 LINC00511 或 LRRC8E 的相互作用。采用 CCK-8、TUNEL 和 Transwell 实验评估 NSCLC 细胞的 IC 值、增殖、迁移和侵袭。
本研究发现，LINC00511 和 LRRC8E 的水平在 NSCLC 组织、顺铂耐药 NSCLC 细胞和非耐药 NSCLC 细胞中升高，而 miR-625 的表达降低。LINC00511 耗竭显著抑制顺铂耐药 NSCLC 细胞的生长、IC 值和转移。此外，抑制 miR-625 可逆转 LINC00511 缺失对 NSCLC 顺铂耐药性的影响。此外，LRRC8E 过表达消除了 miR-625 丰度对顺铂耐药 NSCLC 细胞中 DDP 敏感性的促进作用。
我们的研究结果表明，LINC00511 通过抑制 miR-625 来上调 LRRC8E，从而增加 NSCLC 中的 DDP 耐药性。
