Zhang Rui, Zhang YuanYuan, Li XiaoFei, Wang ShaoHua, Li Jiao, Shao ShuoChun, Liu Bin, Guo WeiWei, Shi Min
Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei Province, People's Republic of China.
Department of Clinical Laboratory, Children's Hospital of Hebei Province, Shijiazhuang, 050031, People's Republic of China.
J Mol Histol. 2025 May 26;56(3):170. doi: 10.1007/s10735-025-10462-y.
Acute T lymphocytic leukemia (T-ALL) is a hematological cancer with high mortality. The literature suggests an association between T-ALL and Long non-coding RNAs (lncRNAs). Nevertheless, the mechanism of lncRNA HOXA11-AS in T-ALL remains undetermined. The lncRNA HOXA11-AS expression level were assessed in T-ALL patients and normal controls by qRT-PCR. Furthermore, The proliferation, apoptosis, and autophagy of T-ALL cell (Molt4 and Jurkat cells) were investigated in vitro via EdU incorporation experiment, flow cytometry, immunofluorescence, and Western blotting. Moreover, the relationship between HOXA11-AS and miR-214-3p and between miR-214-3p, and ATG12 was verified via dual-luciferase reporter assays. Our investigation demonstrated that compared to normal controls, the HOXA11-AS expression level were increased in T-ALL patients. Furthermore, in T-ALL cells, inhibition of HOXA11-AS or overexpression of miR-214-3p reduced autophagy and proliferation, while stimulating apoptosis. However, miR-214-3p inhibition counteracted HOXA11-AS-mediated suppression of T-ALL cell proliferation, autophagy, and apoptosis. In addition, HOXA11-AS modulated ATG12 via sponging miR-214-3p. Overall, this research indicated that lncRNA HOXA11-AS not only stimulates cell proliferation and autophagy but also inhibits apoptosis via the miR-214-3p/ATG12 axis, thereby suggesting that lncRNA HOXA11-AS might be a new candidate for T-ALL diagnosis and therapy.
急性T淋巴细胞白血病(T-ALL)是一种死亡率很高的血液系统癌症。文献表明T-ALL与长链非编码RNA(lncRNA)之间存在关联。然而,lncRNA HOXA11-AS在T-ALL中的作用机制仍未明确。通过qRT-PCR评估T-ALL患者和正常对照中lncRNA HOXA11-AS的表达水平。此外,通过EdU掺入实验、流式细胞术、免疫荧光和蛋白质印迹法在体外研究了T-ALL细胞(Molt4和Jurkat细胞)的增殖、凋亡和自噬。此外,通过双荧光素酶报告基因检测验证了HOXA11-AS与miR-214-3p之间以及miR-214-3p与ATG12之间的关系。我们的研究表明,与正常对照相比,T-ALL患者中HOXA11-AS的表达水平升高。此外,在T-ALL细胞中,抑制HOXA11-AS或过表达miR-214-3p可减少自噬和增殖,同时促进凋亡。然而,抑制miR-214-3p可抵消HOXA11-AS介导的对T-ALL细胞增殖、自噬和凋亡的抑制作用。此外,HOXA11-AS通过海绵吸附miR-214-3p来调节ATG12。总体而言,本研究表明lncRNA HOXA11-AS不仅通过miR-214-3p/ATG12轴刺激细胞增殖和自噬,还抑制凋亡,从而提示lncRNA HOXA11-AS可能是T-ALL诊断和治疗的新候选靶点。