Jin Qiao, Hu Hao, Yan Siqi, Jin Long, Pan Yuliang, Li Xiangjun, Peng Yayi, Cao Peiguo
Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China.
Department of Oncological Radiotherapy, Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, China.
Front Oncol. 2021 Feb 24;11:572585. doi: 10.3389/fonc.2021.572585. eCollection 2021.
With the development of radiotherapy technology, radiotherapy has been increasingly used to treat primary hepatocellular carcinoma (HCC). However, due to radioresistance and the intolerance of the adjacent organs to radiation, the effects of radiotherapy are often unsatisfactory. Therefore, it is necessary to study radiosensitization in HCC.
A microarray was used to analyze the genes that were significantly associated with radiosensitivity. HCC cells, HepG2 and MHCC97H, were subjected to radiation . Real-time PCR was performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression levels. Western blotting was performed to determine histone expression levels. A histone deacetylase (HDAC) whole cell assay was used to determine the activity of HDAC2. MTT, colony formation, 5-ethynyl-2'-deoxyuridine, and wound healing assays were performed to examine the function of MIR22HG and miR-22-5p in cellular radiosensitivity. Chromatin immunoprecipitation-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 of MIR22HG on the radiosensitivity of hepatoma.
Irradiation can up-regulate MIR22HG expression and down-regulate HDAC2 expression. Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression. MIR22HG can increase radiosensitivity miR-22-5p in HCC.
Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby up-regulating the expression of MIR22HG and promoting the production of miR-22-5p, and ultimately increasing the sensitivity of liver cancer radiotherapy.
随着放射治疗技术的发展，放射治疗已越来越多地用于治疗原发性肝细胞癌（HCC）。然而，由于放射抗性以及邻近器官对辐射的不耐受性，放射治疗的效果往往不尽人意。因此，有必要研究HCC中的放射增敏作用。
使用微阵列分析与放射敏感性显著相关的基因。对肝癌细胞HepG2和MHCC97H进行辐射。进行实时聚合酶链反应以确定MIR22HG（微小RNA22宿主基因）和miR-22-5p的表达水平。进行蛋白质免疫印迹以确定组蛋白表达水平。使用组蛋白去乙酰化酶（HDAC）全细胞检测法确定HDAC2的活性。进行MTT、集落形成、5-乙炔基-2'-脱氧尿苷和伤口愈合检测，以研究MIR22HG和miR-22-5p在细胞放射敏感性中的作用。采用染色质免疫沉淀-聚合酶链反应来证实HDAC2影响MIR22HG启动子区域的乙酰化水平。最后，进行动物实验以证明MIR22HG对肝癌放射敏感性的影响。
辐射可上调MIR22HG的表达并下调HDAC2的表达。抑制HDAC2的表达可促进MIR22HG启动子区域的组蛋白乙酰化，并上调MIR22HG的表达。MIR22HG可增加HCC中miR-22-5p的放射敏感性。
抑制HDAC2的表达可促进MIR22HG启动子区域的组蛋白乙酰化，从而上调MIR22HG的表达并促进miR-22-5p的产生，最终提高肝癌放射治疗的敏感性。
