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环状 RNA circ-LDLRAD3 通过海绵吸附 miR-137 上调 SLC1A5 来促进非小细胞肺癌进展,作为一种致癌基因。

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

机构信息

Department of Respiratory Medicine, Minhang Hospital, Fudan University , Shanghai, China.

State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University , Shanghai, China.

出版信息

RNA Biol. 2020 Dec;17(12):1811-1822. doi: 10.1080/15476286.2020.1789819. Epub 2020 Jul 13.

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

摘要

环状 RNA(circRNAs)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 NSCLC 进展的调控仍不清楚。在本研究中,我们发现与正常组织相比,NSCLC 组织和细胞中 circ-LDLRAD3 高表达,miR-137 低表达,且在 NSCLC 组织中呈负相关。进一步的实验验证了 miR-137 可以被 circ-LDLRAD3 在 NSCLC 细胞中海绵吸附和抑制。此外,circ-LDLRAD3 的敲低和 miR-137 的过表达促进 NSCLC 细胞凋亡,并抑制细胞增殖和侵袭。同样,circ-LDLRAD3 的上调或 miR-137 的缺失对上述细胞功能有相反的影响。此外,谷氨酰胺转运体 SLC1A5 被验证为 circ-LDLRAD3 和 miR-137 的下游靶标,上调的 circ-LDLRAD3 通过下调 miR-137 增加 SLC1A5 的表达水平。此外,敲低 circ-LDLRAD3 对细胞增殖、凋亡和迁移的影响均通过敲低 miR-137 和过表达 SLC1A5 而逆转。总之,本研究发现敲低 circ-LDLRAD3 通过调节 miR-137/SLC1A5 轴抑制 NSCLC 的发展。

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