Exosomal circRNA derived from gastric tumor promotes white adipose browning by targeting the miR-133/PRDM16 pathway (Retracted article. See NOV, 2022)
Exosomal circRNA derived from gastric tumor promotes white adipose browning by targeting the miR-133/PRDM16 pathway (Retracted article. See NOV, 2022)
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胃肿瘤来源的外泌体circRNA通过靶向miR-133/PRDM16途径促进白色脂肪褐变
DOI：
10.1002/ijc.31977
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发表时间：
2019-05-15
影响因子：
6.4
通讯作者：
Ba, Yi
中科院分区：
文献类型：
--
作者：
Zhang, Haiyang;Zhu, Lei;Ba, Yi
癌症相关性恶病质是一种代谢综合征，以脂肪和骨骼肌消耗紊乱为特征，并伴有体重减轻和全身炎症。癌症恶病质的治疗选择有限，其分子机制仍知之甚少。环状RNAs(CircRNAs)是一个新的内源性非编码RNAs家族，被认为可以调节哺乳动物的基因表达。外切体是来源于细胞的小囊泡，最近的研究表明CircRNAs在外切体中是稳定的。然而，人们对CircRNAs在外体中的生物学作用知之甚少。在我们的研究中，我们发现血浆外切体中的CircRNAs在胃癌(GC)中具有特异性的表达特征，并且CIRS-133与胃癌患者白色脂肪组织(WAT)的褐变有关。来源于GC细胞的外体将CIRS-133送入前脂肪细胞，通过激活PRDM16和抑制miR-133促进前脂肪细胞向棕色样细胞分化。此外，CIRS-133基因的敲除减少了移植肿瘤小鼠的癌症恶病质，减少了氧气消耗和热量产生。因此，外切体传递的CircRNA参与了Wat褐变，并在癌症相关的恶病质中发挥了关键作用。
Cancer-related cachexia is a metabolic syndrome characterized by a wasting disorder of adipose and skeletal muscle and is accompanied by body weight loss and systemic inflammation. The treatment options for cancer cachexia are limited, and the molecular mechanism remains poorly understood. Circular RNAs (circRNAs) are a novel family of endogenous noncoding RNAs that have been proposed to regulate gene expression in mammals. Exosomes are small vesicles derived from cells, and recent studies have shown that circRNAs are stable in exosomes. However, little is known about the biological role of circRNAs in exosomes. In our study, we showed that circRNAs in plasma exosomes have specific expression features in gastric cancer (GC), and ciRS-133 is linked with the browning of white adipose tissue (WAT) in GC patients. Exosomes derived from GC cells deliver ciRS-133 into preadipocytes, promoting the differentiation of preadipocytes into brown-like cells by activating PRDM16 and suppressing miR-133. Moreover, knockdown of ciRS-133 reduced cancer cachexia in tumor-implanted mice, decreasing oxygen consumption and heat production. Thus, exosome-delivered circRNAs are involved in WAT browning and play a key role in cancer-associated cachexia.