C-MYC Stabilization Is Regulated By TTC36 In Hepatocellular Carcinoma

HCC is the main type of primary liver cancer,and its postoperative recurrence rate is very high and the patient’s prognosis is poor.Therefore,it’s significant to study the mechanism of occurrence and development of HCC for HCC patients.As an oncogene,c-MYC plays an important role in many cellular processes,and promotes the occurrence and development of HCC.Therefore,it’s very helpful to explore the regulatory factor of c-MYC for therapeutic target of HCC patients.In this paper,we identify TTC36 as a positive regulation of c-MYC without affecting the transcription level of cMYC.TTC36 enhanced the stability of c-MYC via decreasing phosphorylated c-MYC at Threonine 58(p-c-MYC(T58))which is phosphorylated by GSK3β and required for c-MYC ubiquitylation and degradation by the proteasome.TTC36 subsequently prevented the polyubiquitylation of c-MYC.Conversely,TTC36 depletion attenuated phosphorylation of GSK3β(S9)and increased p-c-MYC(T58),which was reversed by GSK3 inhibitor BIO.There are lower c-MYC and higher p-cMYC(T58)in TTC36 deficiency mouse.Moreover,overexpression of TTC36 promote the proliferation and migration of HCC cells and increase the number of S-phase cells.The above results indicate that TTC36 may reduce the phosphorylation level of c-MYC(Thr58)by inhibiting the activity of GSK3β,further inhibit the polyubiquitination of c-MYC and function as an pro-tumor factor in HCC cells.