Colorectal cancer prompted adipose tissue browning and cancer cachexia through transferring exosomal miR‐146b‐5p,Journal of Cellular Physiology

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Colorectal cancer prompted adipose tissue browning and cancer cachexia through transferring exosomal miR‐146b‐5p
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-12-27 , DOI: 10.1002/jcp.30245
Wenjuan Di ₁ , Wenling Zhang ₂ , Bei Zhu ₁ , Xiaolin Li ₁ , Qiyun Tang ₁ , Yichan Zhou ₁

Affiliation

Cancer cachexia is a complex syndrome that is associated with thermogenic gene regulation. Currently, although some studies have reported the link between exosomes and cancer cachexia in a few types of cancer, the underlying mechanisms remain poorly understood. In this study, we tried to identify whether exosomes derived from colorectal cancer could affect lipolysis in vitro and in vivo. Here, we collected the tissue samples from 48 patients with colorectal cancer (47.91% females and mean age 55 ± 8.20) and 48 healthy people at the First Affiliated Hospital of Nanjing Medical University to detect the miR‐146‐5p expression. Here, we found that cancer cells released exosomes induced white adipose tissues (WATs) browning and accelerated lipolysis. We also demonstrated that miR‐146b‐5p was enriched in cancer‐related exosomes. Overexpression miR‐146b‐5p resulted in increased WAT browning, decreased oxygen consumption, and fat mass loss (14.57%). The further study identified that miR‐146b‐5p could directly repress the downstream gene homeodomain‐containing gene C10 (HOXC10), thereby regulating lipolysis. Therefore, our results indicated that cancer cells derived from exosomal miR‐146b‐5p played an essential role in WAT browning. Inhibition of cancer‐related exosomes might be necessary for improving the cachexia condition.

中文翻译：

结直肠癌通过转移外泌体 miR-146b-5p 促进脂肪组织褐变和癌症恶病质

癌症恶病质是一种与产热基因调节相关的复杂综合征。目前，尽管一些研究报告了外泌体与几种癌症恶病质之间的联系，但其潜在机制仍知之甚少。在这项研究中，我们试图确定源自结直肠癌的外泌体是否可以影响体外和体内的脂肪分解。本研究收集了南京医科大学第一附属医院 48 例结直肠癌患者（47.91%为女性，平均年龄 55 ± 8.20）和 48 例健康人的组织样本，检测 miR-146-5p 的表达。在这里，我们发现癌细胞释放的外泌体诱导白色脂肪组织（WAT）褐变并加速脂肪分解。我们还证明 miR-146b-5p 在癌症相关的外泌体中富集。过度表达 miR-146b-5p 导致 WAT 褐变增加、耗氧量减少和脂肪量减少 (14.57%)。进一步研究发现，miR-146b-5p可以直接抑制下游基因同源结构域基因C10（HOXC10），从而调节脂肪分解。因此，我们的结果表明，源自外泌体 miR-146b-5p 的癌细胞在 WAT 褐变中发挥着重要作用。抑制癌症相关的外泌体可能对于改善恶病质状况是必要的。

更新日期：2020-12-27

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