International Journal of Molecular Sciences (Jun 2024)
Sorcin Inhibits Mitochondrial Apoptosis by Interacting with STAT3 via NF-κB Pathway
Abstract
Hepatocellular carcinoma (HCC) is a common tumor. Our group has previously reported that sorcin (SRI) plays an important role in the progression and prognosis of HCC. This study aims to explore the mechanism of SRI inhibiting the mitochondrial apoptosis. Bioinformatics analysis, co-IP and immunofluorescence were used to analyze the relationship between SRI and STAT3. MMP and Hoechst staining were performed to detect the effect of SRI on cell apoptosis. The expression of apoptosis-related proteins and NF-κB signaling pathway were examined by Western blot and immunohistochemistry when SRI overexpression or underexpression in vivo and in vitro were found. Moreover, inhibitors were used to further explore the molecular mechanism. Overexpression of SRI inhibited cell apoptosis, which was attenuated by SRI knockdown in vitro and in vivo. Moreover, we identified that STAT3 is an SRI-interacting protein. Mechanistically, SRI interacts with STAT3 and then activates the NF-κB signaling pathway in vitro and in vivo. SRI interacting with STAT3 inhibits apoptosis by the NF-κB pathway and further contributes to the proliferation in HCC, which offers a novel clue and a new potential therapeutic target for HCC.
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