Roles of microRNA-Mediated Drug Resistance in Tumor Stem Cells of Small Cell Lung Carcinoma.

摘要

Lung cancer is the leading cause of cancer deaths in the world, and according to the statistics of National Cancer Institute s SEER, 219,000 men and women will be diagnosed and 159,000 patients will die from this disease in 2014. Small cell lung carcinoma (SCLC) is the cause of approximately 20% of lung cancer. Chemo-therapy is the first choice of treatment for this carcinoma because SCLC is often highly malignant and metastasizes to the distant organs even at an early stage. Although SCLC is chemotherapy-sensitive at the initial stage, it becomes ultimately chemo-resistant with worse prognosis. Recent stem cell theory suggests that there is a distinct population of tumor cells that has stem-cell like characteristics as well as ability of resistance to chemo-therapy. Moreover, several lines of evidence indicated that the self renewal ability of cancer stem cells is regulated by microRNAs. Therefore, we hypothesize that drug resistance of SCLC is mediated by microRNA in tumor stem cell. In this project, we planned to identify the specific microRNA in the stem cells from SCLC. We have established a method to isolate cancer stem cells from human SCLC cell line, and our results indicate that miR16 and 21 are strongly expressed in these CSCs. We also identified five microRNAs (including miR16 and 21) that are involved in Cisplatin resistance by microRNA library screening. Our results strongly suggest that miR16 and miR21 play critical roles in chemo-resistance of cancer stem cell derived from SCLC. Therefore, these oncomirs may serve as potential biomarkers and therapeutic targets for chemoresistant SCLC.