Wang Yu, Zhang Jingqiu, Yang Yu, Chen Jinhao, Tan Fengwu, Zheng Jinfang
Medical and Healthcare Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570102, China.
Department of Dermatology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Heliyon. 2024 Jul 10;10(14):e34438. doi: 10.1016/j.heliyon.2024.e34438. eCollection 2024 Jul 30.
To analyze the expression of mitochondrial translational initiation factor 2 (MTIF2) and the biological functions of the gene in hepatocellular carcinoma (HCC).
The treatment of HCC treatment and its prognostic prediction are limited by a lack of comprehensive understanding of the molecular mechanisms in HCC. : To determine the cells expressing MTIF2 in HCC and the function of the MTIF2+ cell subpopulation.
Gene expression analysis on TIMER 2.0, UALCAN, and GEPIA databases was performed to measure the expression of MTIF2 in HCC tissues. Cell clustering subgroups and annotation were conducted based on the single-cell sequencing data of HCC and paracancerous tissues in the Gene Expression Omnibus (GEO) database. MTIF2 expression in different cell types was analyzed. Further, biological pathways potentially regulated by MTIF2 in each cell type were identified. In addition, protein-protein interaction (PPI) networks of MTIF2 with genes in its regulated biological pathways were developed. The cell function assay was performed to verify the effects of superoxide dismutase-2 (SOD2) and MTIF2 on HCC cells. Finally, we screened virtual drugs targeting MTIF2 and SOD2 employing database screening, molecular docking and molecular dynamics.
MTIF2 showed a remarkably high expression in HCC tissues. We identified a total of 10 cell types between HCC tissues and paracancerous tissues. MTIF2 expression was upregulated in epithelial cells, macrophages, and hepatocytes. More importantly, high-expressed MTIF2 in HCC tissues was mainly derived from epithelial cells and hepatocytes, in which the reactive oxygen species (ROS) pathway was significantly positively correlated with MTIF2. In the PPI network, there was a unique interaction pair between SOD2 and MTIF2 in the ROS pathway. Cell function experiments showed that overexpression of MTIF2 enhanced the proliferative and invasive capacities of HCC, which could synergize with SOD2 to co-promote the development of HCC. Finally, molecular dynamics simulations showed that DB00183 maintained a high structural stability with MTIF2 and SOD2 proteins during the simulation process.
Our study confirmed that the high-expressed MTIF2 in HCC tissues was derived from epithelial cells and hepatocytes. MTIF2 might act on SOD2 to regulate the ROS pathway, thereby affective the progression of HCC.
分析线粒体翻译起始因子2（MTIF2）在肝细胞癌（HCC）中的表达及其生物学功能。
对HCC分子机制缺乏全面了解限制了HCC的治疗及其预后预测。确定HCC中表达MTIF2的细胞以及MTIF2+细胞亚群的功能。
在TIMER 2.0、UALCAN和GEPIA数据库上进行基因表达分析，以测量MTIF2在HCC组织中的表达。基于基因表达综合数据库（GEO）中HCC和癌旁组织的单细胞测序数据进行细胞聚类亚组分析和注释。分析不同细胞类型中MTIF2的表达。此外，确定MTIF2在每种细胞类型中可能调控的生物学途径。此外，构建MTIF2与其调控的生物学途径中的基因的蛋白质-蛋白质相互作用（PPI）网络。进行细胞功能实验以验证超氧化物歧化酶2（SOD2）和MTIF2对HCC细胞的影响。最后，通过数据库筛选、分子对接和分子动力学筛选靶向MTIF2和SOD2的虚拟药物。
MTIF2在HCC组织中显示出显著高表达。我们在HCC组织和癌旁组织之间共鉴定出10种细胞类型。MTIF2在上皮细胞、巨噬细胞和肝细胞中表达上调。更重要的是，HCC组织中高表达的MTIF2主要来源于上皮细胞和肝细胞，其中活性氧（ROS）途径与MTIF2显著正相关。在PPI网络中，ROS途径中SOD2和MTIF2之间存在独特的相互作用对。细胞功能实验表明，MTIF2的过表达增强了HCC的增殖和侵袭能力，其可与SOD2协同促进HCC的发展。最后，分子动力学模拟表明，在模拟过程中DB00183与MTIF2和SOD2蛋白保持高结构稳定性。
我们的研究证实，HCC组织中高表达的MTIF2来源于上皮细胞和肝细胞。MTIF2可能作用于SOD2以调节ROS途径，从而影响HCC的进展。
