ABSTRACT

Circular RNAs (circRNAs) are closely associated with the development of non-small cell lung cancer (NSCLC); however, it is still unclear whether circular RNA circ-LDLRAD3 participated in the regulation of NSCLC progression. In this study, we found that circ-LDLRAD3 was high-expressed and miR-137 was low-expressed in NSCLC tissues and cells compared to their normal counterparts, which showed negative correlations in NSCLC tissues. Further experiments validated that miR-137 could be sponged and inhibited by circ-LDLRAD3 in NSCLC cells. In addition, knock-down of circ-LDLRAD3 and miR-137 overexpression promoted NSCLC cell apoptosis, and inhibited cell proliferation and invasion. Similarly, upregulation of circ-LDLRAD3 or miR-137 ablation had opposite effects on the above cell functions. Besides, the glutamine transporter SLC1A5 was validated to be the downstream target of circ-LDLRAD3 and miR-137, and upregulated circ-LDLRAD3 increased SLC1A5 expression levels by downregulating miR-137. Furthermore, the effects of downregulated circ-LDLRAD3 on cell proliferation, apoptosis and mobility were all reversed by knocking down miR-137 and overexpressing SLC1A5. Taken together, this in vitro study found that knock-down of circ-LDLRAD3 inhibited the development of NSCLC by regulating miR-137/SLC1A5 axis.

摘要

环状RNA（circRNA）与非小细胞肺癌（NSCLC）的发生发展密切相关；然而，circRNA circ-LDLRAD3是否参与了NSCLC进展的调控仍不清楚。在本研究中，我们发现与正常对应物相比，circ-LDLRAD3在NSCLC组织和细胞中高表达而miR-137低表达，这在NSCLC组织中呈负相关。进一步的实验验证了 miR-137 可以在 NSCLC 细胞中被 circ-LDLRAD3 吸收和抑制。此外，敲低 circ-LDLRAD3 和 miR-137 过表达可促进 NSCLC 细胞凋亡，并抑制细胞增殖和侵袭。同样，circ-LDLRAD3 或 miR-137 消融的上调对上述细胞功能具有相反的影响。除了，谷氨酰胺转运蛋白 SLC1A5 被证实是 circ-LDLRAD3 和 miR-137 的下游靶标，并且上调的 circ-LDLRAD3 通过下调 miR-137 来增加 SLC1A5 的表达水平。此外，下调的 circ-LDLRAD3 对细胞增殖、凋亡和迁移率的影响都可以通过敲低 miR-137 和过表达 SLC1A5 来逆转。综合起来，这体外研究发现敲低 circ-LDLRAD3 通过调节 miR-137/SLC1A5 轴抑制 NSCLC 的发展。