Research Paper Volume 14, Issue 14 pp 5783—5799
The miR-590-3p/CFHR3/STAT3 signaling pathway promotes cell proliferation and metastasis in hepatocellular carcinoma
- 1 Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan 430081, Hubei Province, People’s Republic of China
- 2 State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong 0000, People’s Republic of China
- 3 Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 0000, People’s Republic of China
Received: July 15, 2021 Accepted: July 8, 2022 Published: July 18, 2022https://doi.org/10.18632/aging.204178
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Copyright: © 2022 Wan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Accumulating evidence has indicated that Complement factor H-related 3 (CFHR3) plays an essential role in various diseases. However, the biological functions of CFHR3 in hepatocellular carcinoma (HCC) remain largely unclear. Therefore, we perform a further study on CFHR3 in HCC. In this article, we report the suppressive role of CFHR3 in the proliferation and metastasis of HCC cells. CFHR3 downregulation is closely associated with large (T3-T4) HCC, tumor recurrence, and advanced (stage III-IV) clinical stage, functioning as an independent factor for the prognoses of HCC patients. Knockdown of CFHR3 promotes proliferation, migration, and invasion of HCC cells. Mechanistically, downregulation of CFHR3 is induced by miR-590-3p binding to the 3’ untranslated region (UTR) of CFHR3. CFHR3 downregulation promotes the phosphorylation of STAT3 protein, thereby suppressing p53 expression. The promotional effect upon downregulation of CFHR3 induced by CFHR3 stable knockdown or miR-590-3p on HCC cell malignant phenotypes is attenuated by STAT3 inhibitor, S3I-201. In conclusion, our results reveal that CFHR3 is a protective biomarker for HCC patients, and targeting the miR-590-3p/CFHR3/p-STAT3/p53 signaling axis provides a promising strategy for HCC therapeutics.