肺癌是全世界不論男女因癌症致死的的第一名，其中主要的原因是因為肺癌病人往往在診斷出肺癌時已是晚期以及缺乏有效的肺癌治療方式。CISD2在發育生長學中扮演了重要的角色，最常被連結到遺傳疾病（Wolfram 症候群）以及老化的研究。然而CISD2這幾年來在癌症中被廣泛的報導認為是一個致癌基因，包括了乳癌、食道癌、子宮頸癌、咽喉癌以及胃癌等。它在癌症中被認為扮演和癌細胞內的調節氧化壓力平衡以及抑制細胞自噬的角色，而且文獻指出，CISD2的表現量也和病人的預後有關。然而，CISD2在肺癌中扮演的角色仍不清楚也尚未被討論。
我們利用公開之基因表現資料庫及病人檢體的免疫組織染色分析，結果發現，CISD2在肺癌組織的表現量明顯高於周遭正常肺組織。我們也發現，CISD2的mRNA表現量和病人腫瘤的臨床分期和預後有關。在細胞株實驗中，改變CISD2的表現量會影響肺癌細胞的存活、細胞週期、細胞凋亡、細胞侵犯以及粒線體功能。在機轉研究方面，我們發現CISD2的表現量和數個氧化壓力反應基因有負向調控關係，這些基因包括了EGR1與GPX3；而更重要地，上述負向調控關係，也與臨床檢體觀察的結果一致。綜合以上，我們認為CISD2在肺癌生成過程，扮演一個抗氧化基因的角色，可能藉由調控CISD2-ROS-EGR1/GPX3的路徑，進而調控細胞內過高的氧化壓力，以行使其致癌基因功能。藉由標定CISD2達到抑制癌細胞的存活功能可以應用為肺癌病人的治療策略。

Lung cancer is the leading cause of death in cancer in both men and women worldwide. The high mortality of lung cancer mostly can be attributed to diagnosis in late stage and insufficient cancer treatment solutions. CISD2 is a redox-sensitive gene critical for normal development and mitochondrial integrity. CISD2 was known to have aberrant expression in several types of human cancers. However, its relationship with lung cancer is still not clear. In this study, we found CISD2 mRNA was significantly upregulated in lung adenocarcinoma (ADC) samples, compared with their adjacent normal counterparts, and was correlated with tumor stage, grade, and prognosis based on analysis of clinical specimens-derived expression data in public domain and our validation assay. Cell based assay indicated that CISD2 expression regulated accumulation of reactive oxygen species (ROS), polarization of mitochondrial membrane potential, as well as cell viability, apoptosis, invasiveness, and tumorigenicity. In addition, CISD2 expression was found significantly correlated with stress response/redox signaling genes such as EGR1 and GPX3, while such correlations were also found valid in many public domain data. Taken together, upregulation of CISD2 is involved in an increased antioxidant capacity in response to elevated ROS levels during the formation and progression of lung ADC. The molecular mechanism underlying how CISD2 regulates ROS homeostasis and augments malignancy of lung cancer warrants further investigations, and targeting CISD2 is also worthy to be developed as a new strategy to treat lung cancer.

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