Abstract B22: Loss of LncRNA XIST induces Epithelial to Mesenchymal Transition in Breast Cancer

Brain is one of the major sites of metastasis of breast cancer, and approximately 20% of patients with aggressive breast cancer eventually develop the metastatic disease in the brain. Long non-coding RNAs (lncRNA) have recently drawn much attention due to their wide functional variations and potential roles in tumor progression. By performing lncRNA array analysis comparing non-metastatic primary tumors with brain metastatic tumors from breast cancer patients, we identified that lncRNA XIST expression was significantly down-regulated in brain metastatic tumors. The result of Taqman PCR validated the results in tumor samples and also indicated that XIST expression was down-regulated in brain metastatic cell lines compared to non-brain metastatic cell lines. Moreover, we found that the XIST expression was negatively correlated with breast cancer stage and brain metastasis-free survival. XIST is located on the q arm of the X chromosome (Xq13-2) and plays a critical role in the X inactivation, thus providing dosage equivalence between males and females. Importantly, XIST has been found to be down-regulated in several types of tumors including breast cancer. Loss of XIST facilitates escape of some X chromosome genes from inactivation. To further study the effect of XIST down-regulation on tumor cells, we knocked down XIST expression in MCF7 by siRNA. We found that the knockdown of XIST drastically altered the morphology of MCF7 cell from epithelial to mesenchymal type. Furthermore...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Genetics and Evolution of Metastatic Tumors Source Type: research