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Chronic alcohol exposure promotes HCC stemness and metastasis through β-catenin/miR-22-3p/TET2 axis
Journal article   Open access

Chronic alcohol exposure promotes HCC stemness and metastasis through β-catenin/miR-22-3p/TET2 axis

Danlei Chen, Yan Yan, Xinyi Wang, Suzhi Li, Yan Liu, Dandan Yu, Yongjing He, Ruiqing Deng, Yakun Liu, Mei Xu, …
Aging (Albany, NY.), Vol.13(10), pp.14433-14455
05/31/2021
DOI: 10.18632/aging.203059
PMID: 34019487
url
https://doi.org/10.18632/aging.203059View
Published (Version of record) Open Access

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Abstract

Hepatocellular Carcinoma (HCC) patients usually have a high rate of relapse and metastasis. Alcohol, a risk factor for HCC, promotes the aggressiveness of HCC. However, the basic mechanism is still unclear. We used HCC cells and an orthotopic liver tumor model of HCC-LM3 cells for BALB/C nude mice to study the mechanism of alcohol-induced HCC progression. We showed that chronic alcohol exposure promoted HCC cells metastasis and pulmonary nodules formation. First, we identified miR-22-3p as an oncogene in HCC, which promoted HCC cells stemness, tumor growth, and metastasis. Further, we found that miR-22-3p directly targeted TET2 in HCC. TET2, a dioxygenase involved in cytosine demethylation, has pleiotropic roles in hematopoietic stem cells self-renewal. In clinic HCC specimen, TET2 expression was not only decreased by alcohol consumption, but also inversely correlated with miR-22-3p levels. Then, we demonstrated that TET2 depletion promoted HCC cells stemness, tumor growth and metastasis. Furthermore, we identified that β -catenin was an upstream activator of miR-22-3p. In conclusion, this study suggests that chronic alcohol exposure promotes HCC progression and β -catenin/miR-22-3p/TET2 regulatory axis plays an important role in alcohol-promoted HCC malignancy.
 Metastasis alcohol HCC Research Paper stemness

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