The circ-PITX1 promotes non-small cell lung cancer development via the miR-30e-5p/ITGA6 axis.

Wei Li, Pan Yang, Chucheng Zhong, Xiaozhen Shen, Xingyuan Shi, Xiaoping Li

Cell cycle (Georgetown, Tex.) 2022 Feb

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Non-small cell lung cancer (NSCLC) is one of the most prevalent tumors with high incidence and mortality across the globe. Recently, increasing studies have demonstrated that circular RNAs (circRNAs) exert outstanding functions in NSCLC progression. Notwithstanding, we are still in the dark about the function and exact mechanism of circ-PITX1, a newly discovered circRNA. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) confirmed the profile of circ-PITX1 in NSCLC tissues and adjacent normal tissues. Gain- and loss- of function assay verified the impact of circ-PITX1 and miR-30e-5p on the proliferation, invasion, and migration of NSCLC cells (H1975 and A549). Bioinformatics analysis corroborated the downstream mechanisms of circ-PITX1. Dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) examined the interactions between circ-PITX1 and miR-30e-5p, miR-30e-5p and ITGA6. The protein levels of ITGA6, PI3K, AKT were determined by Western blot. circ-PITX1 was substantially up-regulated in NSCLC tissues and cells, and circ-PITX1 up-regulation was correlated with NSCLC patients' poor survival. Functionally, circ-PITX1 overexpression or miR-30e-5p inhibition markedly facilitated proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), reduced apoptosis, and enhanced ITGA6/PI3K/AKT expression in NSCLC cells, whereas circ-PITX1 knockdown or miR-30e-5p up-regulation resulted in the opposite results. Mechanistically, circ-PITX1 acted as a sponge of miR-30e-5p, which targeted the 3'untranslated region (UTR) of ITGA6. Knockdown of circ-PITX1 or overexpressing miR-30e-5p reduced ITGA6/PI3K/AKT axis. circ-PITX1 modulates the miR-30e-5p/ITGA6 axis to boost NSCLC progression, hence functioning as an oncogene.

Citation

Wei Li, Pan Yang, Chucheng Zhong, Xiaozhen Shen, Xingyuan Shi, Xiaoping Li. The circ-PITX1 promotes non-small cell lung cancer development via the miR-30e-5p/ITGA6 axis. Cell cycle (Georgetown, Tex.). 2022 Feb;21(3):304-321