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作 者:夏丹
出 处:《临床医学进展》2019年第10期1163-1173,共11页Advances in Clinical Medicine
基 金:本研究由国家自然科学基金项目(81702776);山东省医药卫生科技发展计划项目(2016WS0569)资助。
摘 要:Membrane-associated RING-CH protein 2 (MARCH2)是MARCH家族成员之一,主要负责囊泡运输,本研究构建了过表达MARCH2和沉默MARCH2的HO-8910细胞系,目的是为了研究MARCH2对卵巢癌细胞自噬及生长的影响。研究发现,沉默MARCH2可以促进自噬体的形成和自噬流,相反,过表达MARCH2会抑制自噬体的形成和自噬流,进一步研究发现,MARCH2缺失介导的自噬作用在ULK1和PIK3C3-BECN1复合物的上游。此外,沉默MARCH2可以抑制体外细胞增殖,亦会抑制体外裸鼠移植瘤的生长。这些效应与自噬信号的活化有关系。MARCH2 is a member of MARCH family, which is mainly responsible for vesicle transport. In this study, we constructed an over-expressed MARCH2 and silenced MARCH2 HO-8910 cell line to study the effect of MARCH2 on the autophagy level of ovarian cancer cells. It was found that knockout of MARCH2 could promote the formation of autophagosome and autophagic flow. On the contrary, overexpression of MARCH2 could inhibit the formation of autophagosome and autophagic flow. Further studies showed that the absence of MARCH2 mediated autophagy upstream of ULK1 and PIK3C3 complexes. In addition, MARCH2 deficiency can inhibit cell proliferation in vitro and the growth of xenografts in nude mice. These effects are related to the activation of autophagic signals.
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