KIF21B acts as an oncogene in hepatocellular carcinoma through the NF- κB/p65 signaling pathway

Research Square (Research Square)(2023)

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摘要
Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Its invasiveness and ability to metastasize contributes to an extremely high patient mortality. However, the molecular mechanisms that underlie the characteristics of HCC progression are not well understood. The kinesin superfamily 21 B (KIF21B) has been shown to be involved in hepatocellular carcinoma (HCC). Nevertheless, its role in HCC has not yet been thoroughly examined. Tumor Genome Atlas (TCGA) was used to analyze the difference of KIF21B expression between HCC and normal tissues and its relationship with clinicopathological features. For further validation, immunohistochemistry (IHC) was used to detect the expression of KIF21B in 116 cases of liver cancer. In vitro studies, we used loss-of-function assays to evaluate the effects of KIF21B and its direct target NF-κB(nuclear factor-κB) p65 subunit on cell growth, proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT).Then the effect of KIF21B inhibition on tumor growth was studied in nude mice in vivo. We demonstrated that elevated KIF21B expression is associated with adverse clinicopathological features, such as tumor size, in HCC patients. In vitro experiments showed that silencing KIF21B could inhibit the proliferation, migration, invasion and EMT of HCC cells, and induce apoptosis, while overexpression of p65 could reverse these effects. In addition, silencing of KIF21B inhibited the growth of HCC in xenografts in nude mice. In this study, we identified and validated that KIF21B plays a carcinogenic role in HCC through NF-κB/p65 signaling pathway, providing a new insight into HCC pathogenesis and therapeutic possibilities.
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hepatocellular carcinoma
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