Li Gang, Gao Lan, Zhao Jing, Liu Dejun, Li Hui, Hu Min
Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Weiwu Road, No. 7, Zhengzhou, Henan 450003 China.
Cancer Cell Int. 2020 Jul 23;20:335. doi: 10.1186/s12935-020-01376-8. eCollection 2020.
Antisense non-coding RNA in the INK4 locus (ANRIL) is of great importance in cell biological behaviors, and ANRIL functions in many kinds of cancers including leukemia. However, the mechanism of ANRIL in the progression of T-cell acute lymphoblastic leukemia (T-ALL) has not been clarified clearly.
qRT-PCR was performed to detect ANRIL expression in T-ALL samples. T-ALL cell lines (MOLT4, CCRF-CEM and KOPT-K1) were used as the cell models. The function of ANRIL on T-ALL cells was investigated by CCK-8 assays, Transwell assays, and apoptosis experiments in vitro. qRT-PCR, Western blot, luciferase reporter assay and RIP assay were used to confirm the interactions between ANRIL and miR-7-5p, miR-7-5p and its target gene transcription factor 4 (TCF4).
ANRIL was significantly up-regulated in T-ALL samples. Its knockdown markedly inhibited viability, migration and invasion of T-ALL cells, but its overexpression exerted the opposite effects. TCF4 was proved to be a target gene of miR-7-5p. ANRIL down-regulated miR-7-5p via sponging it and in turn up-regulated TCF4.
LncRNA ANRIL can modulate malignant phenotypes of T-ALL cells, possibly by regulating miR-7-5p/TCF4 axis, and it serves as a potential therapeutic target for T-ALL.
INK4位点反义非编码RNA(ANRIL)在细胞生物学行为中具有重要意义,并且ANRIL在包括白血病在内的多种癌症中发挥作用。然而,ANRIL在T细胞急性淋巴细胞白血病(T-ALL)进展中的机制尚未完全阐明。
采用qRT-PCR检测T-ALL样本中ANRIL的表达。使用T-ALL细胞系(MOLT4、CCRF-CEM和KOPT-K1)作为细胞模型。通过CCK-8检测、Transwell检测和体外凋亡实验研究ANRIL对T-ALL细胞的作用。采用qRT-PCR、蛋白质免疫印迹法、荧光素酶报告基因检测和RNA免疫沉淀实验来证实ANRIL与miR-7-5p、miR-7-5p与其靶基因转录因子4(TCF4)之间的相互作用。
ANRIL在T-ALL样本中显著上调。敲低ANRIL可显著抑制T-ALL细胞的活力、迁移和侵袭,而过表达则产生相反的效果。证实TCF4是miR-7-5p的靶基因。ANRIL通过海绵吸附作用下调miR-7-5p,进而上调TCF4。
长链非编码RNA ANRIL可能通过调节miR-7-5p/TCF4轴来调节T-ALL细胞的恶性表型,它可作为T-ALL的潜在治疗靶点。