The miR-590-3p/CFHR3/STAT3 signaling pathway promotes cell proliferation and metastasis in hepatocellular carcinoma

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.

Automated summary

CFHR3 plays a suppressive role in HCC cell proliferation and metastasis, with its downregulation associated with aggressive HCC and poor prognosis for patients. The downregulation of CFHR3 is induced by miR-590-3p binding and promotes STAT3 phosphorylation, leading to inhibition of p53 expression. Targeting the miR-590-3p/CFHR3/p-STAT3/p53 signaling axis may provide a promising therapeutic strategy for HCC.