非小细胞肺癌（NSCLC）全球高发。镉是导致肺癌发生的一种重要原因之一，但其作用靶标和发病机制尚不清楚。我们利用基因芯片，从NSCLC组织中选出差异基因TARS2。初步研究发现，TARS2在肺癌中高表达，且与T分期相关，与HMGA1互作可促使mtDNA的转录增加，导致ND2表达增多。研究显示ND2可影响线粒体电子传递链，促进ROS产生，进而激活EGFR及下游通路，促进细胞增殖。进一步蛋白结构分析显示，TARS2极有可能存在独特配体锌，研究发现镉可以替换蛋白内的锌，发挥生物学功能。由此，我们提出重金属镉促进肺癌增殖新机制：镉通过替换TARS2的配体锌，使TARS2与HMGA1互作，上调ND2，干预线粒体电子传递链，促进ROS产生，进而激活EGFR相关通路，促进NSCLC细胞增殖。本项目旨在获得镉诱导TARS2/HMGA1复合体促进NSCLC增殖的可靠证据，为镉诱发肺癌的发病机制提供科学证据。

Non-small-cell lung cancer has a high-occurrence in the world. Heavy metal cadmium is one of the main reason, but its target and nosogenesis mechanisms are unclear. We used gene chip to pick out the differential gene TARS2 from non-small-cell lung cancer tissues.In the preliminary investigation , we found that the TARS2 is highly expressed in non-small-cell lung cancer, and significantly correlated with T stage, and the interaction with HMGA1 can caused the increased transcription of mtDNA. Studies have shown that ND2 have influences on mitochondrial electron transport chain, which can increase the the production of ROS, and ROS can activate the EGFR pathways to promote cell proliferation in non-small cell lung cancer. Through the protein structure analysis of PDB Data Bank, the unique ligands zinc may exist in TARS2, and cadmium can replace zinc within the protein to execute biological function. Taken together, we hypothesize that the new mechanism by which cadmium inducing non-small-cell lung cancer: cadmium replaces zinc in TARS2, promoting TARS2 to interact with HMGA1, thus increasing the ND2 level, then the ND2 interferes with mitochondrial transport chain, raises the level of ROS, and activates EGFR pathways to promote cell proliferation in non-small-cell lung cancer. This project aims to obtain reliable evidence that cadmium induces TARS2/HMGA1 complex to promote the proliferation of non-small-cell lung cancer and provide scientific evidence for the pathogenesis of cadmium-induced non-small-cell lung cancer.