Tang Jianjun, Sun Jing, Liao Jianyun, Pu Chaoke, Yuan Shanshan, Li Chongchong, Chen Jiayin, Shang Lei, Pan Zekai, Chen Jiaqi
Anesthesia Surgery Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
Department of Clinical Nutrition, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Ann Hematol. 2025 Jun;104(6):3389-3401. doi: 10.1007/s00277-025-06354-6. Epub 2025 Jun 23.
Circular RNA (circRNA) is crucial in various biological processes, particularly in the onset and progression of different diseases. Nevertheless, the function of circMUC16 in acute lymphoblastic leukemia (ALL) remains unclear. The expression of circMUC16, miR-1182 and TPPP3 was evaluated by qPCR. The role of circMUC16 in the progression of ALL was investigated bymcherry-EGFP-LC-3, cell cycle, flow cytometry apoptosis, caspase-3 activity, western blotting, and an in vivo xenograft model. The interactions among circMUC16, miR-1182, and TPPP3 were explored by using qPCR, western blot, dual-luciferase reporter, and RNA immunoprecipitation assays.In this study, it was found that circMUC16 was increased in ALL cells. Down-regulation of circMUC16 reduced autophagy, cell proliferation and increased apoptosis in vitro while inhibiting cancer in vivo. circMUC16 acted as a molecular sponge of miR-1182. The carcinogenic effect of circMUC16 was partially mediated by miR-409-3p. TPPP3 was shown to be a direct target of miR-1182 and to be competed with circMUC16. Overexpression of TPPP3 partially counteracted the inhibitory effects of sh-circMUC16 inhibition on malignant behaviors of ALL cells. This study revealed that the circMUC16/miR-1186/TPPP3 axis plays a crucial role in the progression of ALL, suggesting a novel therapeutic target for ALL therapy.
环状RNA（circRNA）在各种生物学过程中至关重要，尤其是在不同疾病的发生和发展过程中。然而，circMUC16在急性淋巴细胞白血病（ALL）中的功能仍不清楚。通过qPCR评估circMUC16、miR-1182和TPPP3的表达。通过mcherry-EGFP-LC-3、细胞周期、流式细胞术凋亡、caspase-3活性、蛋白质印迹以及体内异种移植模型研究circMUC16在ALL进展中的作用。通过使用qPCR、蛋白质印迹、双荧光素酶报告基因和RNA免疫沉淀试验探索circMUC16、miR-1182和TPPP3之间的相互作用。在本研究中，发现ALL细胞中circMUC16增加。circMUC16的下调在体外降低了自噬、细胞增殖并增加了凋亡，同时在体内抑制了癌症。circMUC16充当miR-1182的分子海绵。circMUC16的致癌作用部分由miR-409-3p介导。TPPP3被证明是miR-1182的直接靶标，并与circMUC16相互竞争。TPPP3的过表达部分抵消了sh-circMUC16抑制对ALL细胞恶性行为的抑制作用。本研究揭示了circMUC16/miR-1186/TPPP3轴在ALL进展中起关键作用，为ALL治疗提出了新的治疗靶点。
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