Circular RNA LDLRAD3 behaved as an oncogene in several malignancies, but its effects in NSCLC and the involvement of downstream molecules and activation of signaling pathways had not been fully reported. We planned to explore how LDLRAD3 facilitated the malignancy of NSCLC. QRT-PCR was performed to evaluate the expression levels of LDLRAD3, miR-20a-5p, and SLC7A5 in NSCLC tissues and cells. si-LDLRAD3 was transfected to A549 and H1299 cells to knock down intrinsic LDLRAD3 to determine its oncogenic roles. CCK-8 assay and transwell assay were executed to assess cell proliferative, migrative, and invasive abilities. Dual-luciferase reporter (DLR) assay was manipulated to verify the ENCORI-predicted relationships between LDLRAD3 and miR-20a-5p and between miR-20a-5p and SLC7A5. Western blot, immunofluorescent assay, and immunohistochemistry were applied to explore the expression levels of SLC7A5, and the levels of mTORC1 pathway-related proteins were evaluated using western blot. Rescue experiments were conducted by transfecting si-LDLRAD3, miR-20a-5p inhibitor, and si-SLC7A5 to explore the influence of the LDLRAD3-miR-20a-5p-SLC7A5 axis on the malignant behaviors of NSCLC cells. The expression levels of LDLRAD3 and SLC7A5 were boosted, whereas miR-20a-5p was impeded in NSCLC tissues and cell lines. Knockdown of LDLRAD3 weakened the proliferation, migration, and invasion of A549 and H1299 cells. LDLRAD3 was verified to sponge miR-20a-5p and miR-20a-5p targeted SLC7A5. LDLRAD3 activated the mTORC1 singling pathway via the miR-20a-5p-SLC7A5 axis to strengthen the malignant properties of A549 and H1299 cells. We concluded that LDLRAD3 exerted oncogenic effects via the miR-20a-5p-SLC7A5 axis to activate the mTORC1 signaling pathway in NSCLC. Our findings enlightened that LDLRAD3 could become a potential therapeutic target in the treatment and management of NSCLC.
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