Thoracic Cancer (Dec 2023)
Circ_0102231 inactivates the PI3K/AKT signaling pathway by regulating the miR‐635/NOVA2 pathway to promote the progression of non‐small cell lung cancer
Abstract
Abstract Background Circular RNAs (circRNAs) are involved in the malignant development of tumors. However, the mechanism of circ_0102231 in non‐small cell lung cancer (NSCLC) has rarely been discussed and reported. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to measure the expression of circ_0102231, miR‐635 and NOVA alternative splicing regulator 2 (NOVA2) in NSCLC tissues and cells. Western blot was applied to detect the protein expression. Cell proliferation was monitored by cell counting kit‐8 (CCK8) and 5‐ethynyl‐2′‐deoxyuridine (EdU) experiments. The angiogenesis ability of cells was tested by angiogenesis assay. Flow cytometry was used to analyze cell apoptosis. The relationship between circ_0102231 and NOVA2 or miR‐635 was analyzed by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. An in vivo transplanted tumor model was established to confirm the effect of circ_0102231 on tumor formation. Results Circ_0102231 was abnormally upregulated in NSCLC tissues and correlated with clinical stage. Silencing of circ_0102231 inhibited cell proliferation and angiogenesis but significantly promoted the apoptosis of NSCLC cells. There were target binding sites between circ_0102231 and miR‐635, miR‐635 and NOVA2. Importantly, circ_0102231 acted as a sponge for miR‐635, increased the expression of NOVA2, and activated the PI3K/AKT signaling pathway. Finally, silencing of circ_0102231 also had obvious antitumor effects in vivo. Conclusion Circ_0102231 increased the expression of NOVA2 by interacting with miR‐635 to promote the malignant progression of NSCLC.
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