[摘 要] 目的：探究环状RNA（circRNA）调控舌鳞状细胞癌（TSCC）顺铂（CDDP）耐药的机制。方法：本研究以TSCC化疗敏感CAL27细胞与耐药CAL27-res细胞为研究对象，RT-qPCR检测两种细胞内hsa_circ_0034762的表达量差异，流式细胞术检测细胞凋亡率，Western blotting检测自噬相关蛋白p62及LC3-Ⅱ/LC3-Ⅰ比值，透射电镜观察自噬小体的数量，双萤光素酶报告实验检测hsa_circ_0034762与miR-17-3p的结合关系，荧光原位杂交实验检测二者在细胞中的共定位，敲低hsa_circ_0034762联合抑制miR-17-3p进行功能回复实验。结果：相比亲本化疗敏感细胞，TSCC耐药细胞CAL27-res自噬水平显著提升，表现为自噬小体数量增加、LC3-Ⅱ/LC3-Ⅰ比值升高及p62蛋白表达降低。hsa_circ_0034762在TSCC耐药组织及CAL27-res细胞中高表达。敲低hsa_circ_0034762后，CAL27-res细胞凋亡率升高，自噬小体数量减少，p62蛋白表达增加，LC3-Ⅱ/LC3-Ⅰ比值降低（均P < 0.05）。 双萤光素酶报告实验与荧光原位杂交实验发现hsa_circ_0034762与miR-17-3p存在靶向结合作用。抑制miR-17-3p可部分逆转hsa_circ_0034762敲低所致的促凋亡及抑制自噬效应。结论：hsa_circ_0034762在TSCC耐药细胞及组织中高表达。敲低hsa_circ_0034762可能通过miR-17-3p抑制细胞自噬并促进细胞凋亡，从而降低TSCC细胞的化疗耐药性。

[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.

[基金项目] 国家自然科学基金（81903045）