hsa_circ_0034762 contributes to cisplatin resistance in tongue squamous cell carcinoma CAL27-res cells via miR-17-3p-mediated regulation of autophagy
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Abstract:
[Abstract] Objective: To elucidate the mechanism by which circular RNA (circRNA) regulates cisplatin (CDDP) resistance in tongue squamous cell carcinoma (TSCC). Methods: Chemosensitive and chemoresistant TSCC cells were used in this study. The differential expression of hsa_circ_0034762 in CAL27 and CAL27-res cells was detected by RT-qPCR. Cell apoptosis was evaluated by flow cytometry, and the autophagy-related protein p62, the LC3- Ⅱ/LC3- Ⅰ ratio were determined by Western blotting. The number of autophagosomes was observed by transmission electron microscopy (TEM). The targeting relationship between hsa_circ_0034762 and miR-17-3p was verified using a dual-luciferase reporter assay, and their co-localization in cells was detected by fluorescence in situ hybridization (FISH). Functional rescue experiments were performed by knocking down hsa_circ_0034762 alone or in combination with miR-17-3p inhibition. Results: Compared with parental chemosensitive cells, CAL27-res cells displayed significantly increased autophagy, as evidenced by an increased number of autophagosomes, an elevated LC3-Ⅱ/LC3-Ⅰ ratio, and decreased p62 protein expression. hsa_circ_0034762 was highly expressed in both chemoresistant TSCC tissues and CAL27-res cells. Knockdown of hsa_circ_0034762 significantly increased the apoptosis rate of CAL27-res cells, reduced the number of autophagosomes, upregulated p62 expression, and decreased the LC3-Ⅱ/LC3-Ⅰ ratio (all P < 0.05). Dual-luciferase reporter and FISH assays confirmed the targeted binding between hsa_circ_0034762 and miR-17-3p. Inhibition of miR-17-3p partially reversed the pro-apoptotic and autophagy- suppressive effects induced by hsa_circ_0034762 knockdown. Conclusion: hsa_circ_0034762 is overexpressed in chemoresistant TSCC tissues and cells. Knockdown of hsa_circ_0034762 suppresses autophagy and promotes apoptosis through miR-17-3p-mediated · · 651 [[PAGE_INDEX=2 FILE=7f0b8458-32b0-497d-b515-1deca828e6eb.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) regulation, thereby reducing the chemoresistance of TSCC cells.