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MicroRNA-365 induces apoptosis and inhibits invasion of human myeloma cells by targeting homeobox A9 (HOXA9)
Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2021-02-20 , DOI: 10.1016/j.etap.2021.103627
Ying Gao 1 , Yudi Miao 1 , Weihua Zhang 1 , Xingli Ru 1 , LiMin Hou 1
Affiliation  

The aberrant micro-RNA (miR) expression has been reported to play a vital role in proliferation and tumorigenesis and of several human cancers. MicroRNA-365 (miR-365) has been shown to exhibit tumor-suppressive or oncogenic role in several human cancers. Nonetheless, little is known about its growth regulatory role in human multiple myeloma. The present study characterized the regulatory control exercised by miR-365 in multiple myeloma. The results showed significant (P < 0.05) upregulation of miR-365 in myeloma tissues and cell lines. Overexpression of miR-365 significantly (P < 0.05) suppressed the proliferation and inhibition of miR-365 promoted the proliferation of the human myeloma cells. The tumor-suppressive effects of miR-365 were found to be the result of apoptosis in the IM-9 myeloma cells. The miR-365 overexpression also suppressed the invasion of the IM-9 myeloma cells. The homeobox gene, HOXA9 was identified as the molecular regulatory target of miR-365 in human myeloma. The overexpression of miR-365 was shown to cause suppression of HOXA9. The silencing of HOXA9 could also suppress the growth of the IM-9 myeloma cells while as the overexpression of HOXA9 could abolish the tumor-suppressive effects of miR-365. The in vivo study revealed that miR-365 inhibits the growth of the xenografted tumors. Nonetheless, the inhibition of miR-365 promotes the growth of the xenografted tumors. To sum up, the current study suggests the tumor-suppressive effects of miR-365 in human myeloma and highlights the applicability of miR-365 as vital therapeutic target against this fatal malignancy.



中文翻译:


MicroRNA-365 通过靶向同源框 A9 (HOXA9) 诱导细胞凋亡并抑制人骨髓瘤细胞的侵袭



据报道,异常的 micro-RNA (miR) 表达在增殖和肿瘤发生以及多种人类癌症中发挥着至关重要的作用。 MicroRNA-365 (miR-365) 已被证明在多种人类癌症中表现出肿瘤抑制或致癌作用。尽管如此,人们对其在人类多发性骨髓瘤中的生长调节作用知之甚少。本研究描述了 miR-365 在多发性骨髓瘤中发挥的调控作用。结果显示,骨髓瘤组织和细胞系中 miR-365 显着上调(P < 0.05)。 miR-365的过表达显着(P < 0.05)抑制人骨髓瘤细胞的增殖,抑制miR-365促进人骨髓瘤细胞的增殖。研究发现 miR-365 的肿瘤抑制作用是 IM-9 骨髓瘤细胞凋亡的结果。 miR-365 过表达还抑制 IM-9 骨髓瘤细胞的侵袭。同源框基因 HOXA9 被确定为人骨髓瘤中 miR-365 的分子调控靶点。 miR-365 的过度表达被证明会导致 HOXA9 的抑制。 HOXA9 的沉默还可以抑制 IM-9 骨髓瘤细胞的生长,而 HOXA9 的过表达可以消除 miR-365 的肿瘤抑制作用。体内研究表明miR-365抑制异种移植肿瘤的生长。尽管如此,miR-365 的抑制促进了异种移植肿瘤的生长。综上所述,目前的研究表明 miR-365 在人类骨髓瘤中具有肿瘤抑制作用,并强调 miR-365 作为针对这种致命恶性肿瘤的重要治疗靶点的适用性。

更新日期:2021-03-16
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