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微小RNA-320a通过靶向前B细胞白血病转录因子3调控多发性骨髓瘤细胞的增殖和凋亡。

miR-320a regulates cell proliferation and apoptosis in multiple myeloma by targeting pre-B-cell leukemia transcription factor 3.

作者信息

Lu Yinghao, Wu Depei, Wang Jishi, Li Yan, Chai Xiao, Kang Qian

机构信息

Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, 215006, China; Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province, China.

Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, 215006, China.

出版信息

Biochem Biophys Res Commun. 2016 May 13;473(4):1315-1320. doi: 10.1016/j.bbrc.2016.04.069. Epub 2016 Apr 14.

Abstract

Aberrant expression of microRNAs (miRNAs) is implicated in cancer development and progression. While miR-320a is reported to be deregulated in many malignancy types, its biological role in multiple myeloma (MM) remains unclear. Here, we observed reduced expression of miR-320a in MM samples and cell lines. Ectopic expression of miR-320a dramatically suppressed cell viability and clonogenicity and induced apoptosis in vitro. Mechanistic investigation led to the identification of Pre-B-cellleukemia transcription factor 3 (PBX3) as a novel and direct downstream target of miR-320a. Interestingly, reintroduction of PBX3 abrogated miR-320a-induced MM cell growth inhibition and apoptosis. In a mouse xenograft model, miR-320a overexpression inhibited tumorigenicity and promoted apoptosis. Our findings collectively indicate that miR-320a inhibits cell proliferation and induces apoptosis in MM cells by directly targeting PBX3, supporting its utility as a novel and potential therapeutic agent for miRNA-based MM therapy.

摘要

微小RNA(miRNA)的异常表达与癌症的发生和发展有关。虽然据报道miR-320a在多种恶性肿瘤类型中表达失调,但其在多发性骨髓瘤(MM)中的生物学作用仍不清楚。在此,我们观察到MM样本和细胞系中miR-320a表达降低。miR-320a的异位表达显著抑制细胞活力和克隆形成能力,并在体外诱导细胞凋亡。机制研究发现前B细胞白血病转录因子3(PBX3)是miR-320a新的直接下游靶点。有趣的是,重新引入PBX3可消除miR-320a诱导的MM细胞生长抑制和凋亡。在小鼠异种移植模型中,miR-320a过表达抑制肿瘤发生并促进细胞凋亡。我们的研究结果共同表明,miR-320a通过直接靶向PBX3抑制MM细胞增殖并诱导细胞凋亡,支持其作为基于miRNA的MM治疗的新型潜在治疗剂的效用。

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