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Exosome circRNA secreted from adipocytes promotes the growth of hepatocellular carcinoma by targeting deubiquitination-related USP7.

Haiyang Zhang | Ting Deng | Shaohua Ge | Ying Liu | Ming Bai | Kegan Zhu | Qian Fan | Jialu Li | Tao Ning | Fei Tian | Hongli Li | Wu Sun | Guoguang Ying | Yi Ba
Oncogene | 2019

Hepatocellular carcinoma (HCC), the major form of liver cancer, has shown increasing incidence and poor prognosis. Adipose tissue is known to function in energy storage and metabolism regulation by the secretion of adipokines. Circular RNAs (circRNAs), a novel type of noncoding RNA, have recently been recognized as key factors in tumor development, but the role of exosome circRNAs derived from adipose tissues has not been defined yet. Here, adipose-secreted circRNAs were found to regulate deubiquitination in HCC, thus facilitating cell growth. It was observed that exosome circ-deubiquitination (circ-DB) is upregulated in HCC patients with higher body fat ratios. Moreover, in vitro and in vivo studies showed that exo-circ-DB promotes HCC growth and reduces DNA damage via the suppression of miR-34a and the activation of deubiquitination-related USP7. Finally, the results showed that the effects of adipose exosomes on HCC cells can be reversed by knockdown of circ-DB. These results indicate that exosome circRNAs secreted from adipocytes promote tumor growth and reduce DNA damage by suppressing miR-34a and activating the USP7/Cyclin A2 signaling pathway.

Pubmed ID: 30546088

Research resources used in this publication

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Antibodies used in this publication

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Associated grants

  • Agency: National Natural Science Foundation of China (National Science Foundation of China), International
    Id: 81772629

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