Shaanxi Provincial People's Hospital, Xi'an, Shaanxi Province, China.
Department of Hematology, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Aging (Albany NY). 2021 Oct 25;13(20):23757-23768. doi: 10.18632/aging.203647.
Circular RNAs (circRNAs) have demonstrated critical roles in the development of cancers. This study aimed to explore the function of circular RNA circPRKCI/miR-20a-5p/SOX4 axis in acute lymphoblastic leukemia (ALL). Our data showed that the expression of circPRKCI and SOX4 was enhanced while the expression of miR-20a-5p was reduced in the clinical T-ALL samples. The expression of miR-20a-5p was negatively associated with circPRKCI and SOX4 in the T-ALL patients and the expression of circPRKCI was positive correlated with SOX4 in the T-ALL patients. Functionally, the silencing of circPRKCI suppressed the viability of T-ALL cells. Conversely, the knockdown of circPRKCI promoted the apoptosis of T-ALL cells. The levels of cleaved PARP and cleaved caspase3 were induced by the depletion of circPRKCI in T-ALL cells. Mechanically, the luciferase activity of circPRKCI was significantly decreased in T-ALL cells after the treatment of miR-20a-5p mimic. Meanwhile, the silencing of circPRKCI promoted the expression of miR-20a-5p in T-ALL cells, implying that circPRKCI serves as a competitive endogenous RNAs (ceRNA) of miR-20a-5p. We validated that the treatment of miR-20a-5p mimic inhibited the viability of T-ALL cells. MiR-20a-5p mimic enhanced the apoptosis of T-ALL cells. The expression of cleaved PARP and cleaved caspase3 was increased by miR-20a-5p mimic in the cells. In summarization, we concluded that circular RNA circPRKCI contributed to malignant progression of T-cell acute lymphoblastic leukemia by modulating miR-20a-5p/SOX4 axis. Targeting circPRKCI may serve as a promising therapeutic strategy of T-ALL.
环状 RNA(circRNAs)在癌症的发展中发挥了关键作用。本研究旨在探讨环状 RNA circPRKCI/miR-20a-5p/SOX4 轴在急性淋巴细胞白血病(ALL)中的功能。我们的数据显示,在临床 T-ALL 样本中,circPRKCI 和 SOX4 的表达增强,而 miR-20a-5p 的表达降低。在 T-ALL 患者中,miR-20a-5p 的表达与 circPRKCI 和 SOX4 呈负相关,而 circPRKCI 的表达与 T-ALL 患者中的 SOX4 呈正相关。功能上,circPRKCI 的沉默抑制了 T-ALL 细胞的活力。相反,circPRKCI 的敲低促进了 T-ALL 细胞的凋亡。在 T-ALL 细胞中,circPRKCI 的耗竭诱导了 cleaved PARP 和 cleaved caspase3 的水平增加。机制上,miR-20a-5p 模拟物处理后 T-ALL 细胞中 circPRKCI 的荧光素酶活性显著降低。同时,circPRKCI 的沉默促进了 T-ALL 细胞中 miR-20a-5p 的表达,表明 circPRKCI 作为 miR-20a-5p 的竞争性内源性 RNA(ceRNA)。我们验证了 miR-20a-5p 模拟物的处理抑制了 T-ALL 细胞的活力。miR-20a-5p 模拟物增强了 T-ALL 细胞的凋亡。在细胞中,miR-20a-5p 模拟物增加了 cleaved PARP 和 cleaved caspase3 的表达。综上所述,我们得出结论,环状 RNA circPRKCI 通过调节 miR-20a-5p/SOX4 轴促进 T 细胞急性淋巴细胞白血病的恶性进展。靶向 circPRKCI 可能是治疗 T-ALL 的一种有前途的策略。