lncRNA MIR22HG Derived miR-22-5p Enhanced Radiosensitivity of Hepatocellular Carcinoma by Increasing Histone Acetylation Via Inhibiting HDAC2 Activity

Background: With the development of radiotherapy technology, Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma (HCC). But due to the radioresistance and the intolerance of the adjacent organs, the effect of radiotherapy is not satisfactory. Therefore, it is necessary to study the radiosensitization of HCC. Method: Microarray was used to analyze the significant gene associated with radiosensitivity. Application of HCC cells HepG2 and MHCC97H in vitro. Real-time PCR performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression, western blot performed to determine histone expression. HDAC whole cell assay was sed to determine the activity of HDAC2. Then, MTT, colony formation, EDU, wound healing assays were to examine the function of MIR22HG and miR-22-5p on cellular radiosentivity. ChIP-PCR was used to confirm that HDAC2 affects the acetylation level of the MIR22HG promoter region. Finally, animal experiments were performed to demonstrate the effect MIR22HG on the radiosensitivity of hepatoma in vivo. Results: Irradiation can upregulate MIR22HG expression and downregulate HDAC2 expression; Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression; MIR22HG can increase radiosensitivity via miR-22-5p in HCC. Conclusion: Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby upregulating the expression of MIR22HG and promoting the production of miR-22-5p, ultimately increasing the sensitivity of liver cancer radiotherapy. Funding: This work was supported by the National Natural Science Foundation of China (81872473), Key R & D projects of Hunan science and technology planning project (2017SK2052). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: All experiments were approved by the Animal Center of China South University and performed following International Guidelines and Protocols.