CircEPSTI1 Promotes the Progression of Non-Small Cell Lung Cancer Through miR-145/HMGB3 Axis

BACKGROUND: The high expression of circular RNA circEPSTI1 (hsa_circRNA_000479) has been reported to be associated with the malignant potential of ovarian cancer cells and triple-negative breast cancer cells. However, the expression profile and function of circEPSTI1 in non-small cell lung cancer (NSCLC) are not fully addressed. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to measure the RNA expression of circEPSTI1, relevant microRNAs (miRNAs) and high mobility group box 3 (HMGB3) in NSCLC tissues and cells. Cell counting kit 8 (CCK8) assay, colony formation and transwell assays were conducted to detect the capacities of proliferation, colony formation and metastasis in NSCLC cells. Western blot assay was performed to detect the expression of metastasis-associated proteins and HMGB3. Animal experiment was carried out to confirm the function of circEPSTI1 in vivo. The combination between miR-145 and circEPSTI1 or HMGB3 was verified by dual-luciferase reporter assay, RNA pull-down and RIP assays. RESULTS: CircEPSTI1 was abnormally up-regulated in NSCLC tissues and cells in comparison with that in normal tissues and cells. The high expression of circEPSTI1 was associated with the low survival rate of NSCLC patients. CircEPSTI1 accelerated the proliferation, colony formation and motility of NSCLC cells in vitro. CircEPSTI1 silencing restrained the NSCLC tumor growth in vivo. miR-145 was validated as a target of circEPSTI1 in NSCLC cells. HMGB3 was a direct downstream target of miR-145 in NSCLC cells. The decreased abilities of proliferation, colony formation and metastasis caused by the silencing of circEPSTI1 were reversed by the depletion of miR-145 or the accumulation of HMGB3 in NSCLC cells. CONCLUSION: CircEPSTI1 aggravated the progression of NSCLC through elevating the expression of HMGB3 via sponging miR-145.