Circular RNA circ-LDLRAD3 serves as an oncogene to promote non-small cell lung cancer progression by upregulating SLC1A5 through sponging miR-137

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 <i>in vitro</i> study found that knock-down of circ-LDLRAD3 inhibited the development of NSCLC by regulating miR-137/SLC1A5 axis.

环状RNA（circRNAs）与非小细胞肺癌（NSCLC）的发生发展密切相关，但目前尚不明确环状RNA circ-LDLRAD3是否参与调控非小细胞肺癌的进展。本研究发现，相较于正常对照组织与细胞，非小细胞肺癌组织及细胞中circ-LDLRAD3呈高表达，而miR-137呈低表达，且二者在非小细胞肺癌组织中呈负相关。后续实验证实，在非小细胞肺癌细胞中，circ-LDLRAD3可通过海绵吸附作用抑制miR-137的功能。此外，敲低circ-LDLRAD3并过表达miR-137可促进非小细胞肺癌细胞凋亡，同时抑制细胞增殖与侵袭能力。与之相反，过表达circ-LDLRAD3或敲低miR-137则对上述细胞功能产生相反的调控效果。此外，谷氨酰胺转运蛋白SLC1A5被证实为circ-LDLRAD3与miR-137的下游靶标，过表达circ-LDLRAD3可通过下调miR-137的水平升高SLC1A5的表达量。进一步研究发现，敲低circ-LDLRAD3对细胞增殖、凋亡及迁移能力产生的调控作用，可通过敲低miR-137并过表达SLC1A5得以逆转。综上，本项体外研究表明，敲低circ-LDLRAD3可通过调控miR-137/SLC1A5轴抑制非小细胞肺癌的发生发展。