The Role And Molecular Mechanism Of FAM111 Trypsin Like Peptidase B(FAM111B) In The Progression Of Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma(HCC)is not only one of the most common solid malignant tumors,but a crucial cause of cancer-related death in the world.The existing treatments are not enough to completely eradicate HCC.Therefore,there is a pressing need to seek out new and effective biomarkers to evaluate the prognosis of patients with HCC and improve the effectiveness of treatment strategies.FAM111 trypsin-like peptidase B(FAM111B)is a serine-like protease characterized by the trypsin-like serine/cysteine peptidase domain at the C-terminal of the protein.The abnormal expression of FAM111B has been found to be related to the occurrence,development and prognosis of breast cancer,lung cancer and other tumors.However,the pathological role and specific biological function of FAM111B in HCC are not clear.This study aims to explore the role of FAM111B in HCC and its regulatory mechanism.MethodsTCGA database,qRT-PCR and immunohistochemistry were used to detect the expression level of FAM111B in HCC.Lentivirus transfection was used to construct FAM111B knockout HCC cells.The biological role of FAM111B in HCC cells was investigated by cell counting kit 8(CCK-8),colony formation,transwell,wound healing and flow cytometry.The levels of p38 mitogen-activated protein kinase(MAPK)and its related proteins were detected by Western blot.The interaction between FAM111B and mitofusins 2(MFN2)was detected by coimmunoprecipitation assay,and the binding of cAMP-response element binding protein(CREB)and decapping Enzyme 1A(DCP1A)chromatin was determined by chromatin co-precipitation technique.ResultsFirst,we demonstrated that FAM111B was highly expressed in HCC.Besides,FAM111B high expression was also an independent risk factor for poor prognosis in patients with HCC.In vivo and in vitro experiments showed that down-regulation of FAM111B could inhibit the proliferation,migration,invasion and anti-apoptosis of HCC cells.Further studies showed that FAM111B could interact with MFN2 and down-regulate the expression of MFN2.Importantly,the interaction between FAM111B and MFN2 could activate the p38 MAPK signal pathway and then activate the transcription factor CREB.In addition,activated CREB upregulated the expression of DCP1A in HCC,thus promoting the malignant progression of HCC.ConclusionsWe confirmed that FAM111B expression is upregulated in HCC and,which is associated with poor prognosis in HCC patients.And we elucidated the mechanism by which FAM111B regulates the p38 MAPK/CREB/DCP1A signaling axis by interacting with MFN2 and downregulating MFN2 expression,ultimately promoting the malignant progression of HCC.Therefore,FAM111B can be regarded as a potential target for the treatment and prognosis of HCC.