MicroRNA miR-188-5p as a mediator of long non-coding RNA MALAT1 regulates cell proliferation and apoptosis in multiple myeloma.

MicroRNA miR-188-5p as a mediator of long non-coding RNA MALAT1 regulates cell proliferation and apoptosis in multiple myeloma.
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DOI:
10.1080/21655979.2021.1920325
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发表时间:
2021-12
期刊:
影响因子:
4.9
通讯作者:
Yang W
Yang W
中科院分区:
生物学2区
文献类型:
--
作者:
Liu H;Chi Z;Jin H;Yang W

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多发性骨髓瘤(MM)是一种主要来源于骨髓的浆细胞恶性肿瘤,一般仍无法治愈。据报道,LncRNA MALAT 1在MM细胞中上调,并且MALAT 1的敲低抑制MM细胞周期进展并增强细胞凋亡。在线靶点预测显示,miR-188- 5 p中存在MALAT 1的两个靶点,miR-188- 5 p已被鉴定为其他类型癌症的肿瘤抑制因子。然而,miR-188- 5 p在MM中的作用以及miR-188- 5 p是否介导由MALAT 1调控的MM肿瘤进展仍然未知。本研究以四种主要的MM细胞系为研究对象,通过转染miR-188 - 5 p模拟物/抑制剂以及miR-188 - 5 p抑制剂与MALAT 1-shRNA质粒共转染,研究miR-188 - 5 p对MM细胞增殖和凋亡的影响。并建立异种移植瘤模型,在体内研究这些作用。miR-188- 5 p的过表达可抑制MM细胞的活力、增殖和肿瘤生长,并使细胞周期阻滞于G1期至S期,而miR-188- 5 p的敲低则在体内外均表现出相反的作用。此外,MALAT 1通过直接结合miR-188 - 5 p与miR-188 - 5 p表达呈负相关,而miR-188- 5 p可介导MALAT 1调控的MM细胞增殖和凋亡。这些发现表明miR-188- 5 p在MM的进展中作为肿瘤抑制因子,并直接参与由MALAT 1调节的MM细胞增殖和凋亡,这可能为MM的临床治疗提供潜在的治疗靶点或预后指标。
Multiple myeloma (MM), a malignancy of plasma cells mainly derived from the bone marrow, has remained incurable generally. LncRNA MALAT1 has been reported to be upregulated in the MM cells and knockdown of MALAT1 inhibited MM cell cycle progression and enhanced cell apoptosis. Online target prediction showed that two target sites for MALAT1 existed in miR-188-5p, which has been identified as a tumor suppressor in other types of cancers. However, the role of miR-188-5p in the MM and whether miR-188-5p mediates the MM tumor progression regulated by MALAT1 are still unknown. Herein, four main MM cell lines were adopted to investigate the effects of miR-188-5p on cell proliferation and apoptosis via transfection with miR-188-5p mimic/inhibitor and co-transfection with miR-188-5p inhibitor and MALAT1-shRNA plasmids. Xenograft tumor model was also established to study these effects in vivo. Overexpression of miR-188-5p inhibited cell viability, cell proliferation as well as tumor growth and arrested cell cycle at G1 to S transition, but miR-188-5p knockdown showed opposite effects on the MM cells in vitro and in vivo. Moreover, MALAT1 was shown to be inversely correlated with miR-188-5p expression through direct binding to miR-188-5p, and in turn, miR-188-5p could mediate the MM cell proliferation and apoptosis regulated by MALAT1. These findings indicate that miR-188-5p serves as a tumor suppressor in the progression of the MM and is directly involved in MM cell proliferation and apoptosis regulated by MALAT1, which may provide a potential therapeutic target or prognostic indictor for MM clinical treatment.
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