Professor UTHSCSA San Antonio, Texas, United States
Background: Renal cell carcinoma (RCC) is the 6th leading cause of cancer in men and the 8th among women in the U.S. Approximately 50% of patients with metastatic RCC have a survival rate less than a year. Little is known about the molecular mechanisms that promote tumorigenesis in RCC. Therefore, identifying new genes and pathways that contribute to RCC progression and developing strategies to target the biological pathways that are dependent on these genes will constitute the basis for devising new therapies to treat RCC patients.
Methods: We performed RNA-seq studies using biopsies from RCC patients . In addition we used several RCC cell lines as well as NEGR1 knockout cell line and overexpressing NEGR1 in human proximal tubular cells. Moreover, cells deficient in NEGR1 treated with rapamycin or sunitinib to measure cell migration and cell invasion.
Results: Our ongoing RNA-seq studies using biopsies from RCC patients discovered a new tumor suppressor gene, Neuronal Growth Regulator 1 (NEGR1) that is associated with RCC. TCGA data also confirm that NEGR1 mutations are associated with low survival in RCC patients. Our preliminary studies demonstrate that NEGR1 is significantly decreased in biopsies from RCC patients and in different RCC cell lines. In addition, NEGR1 knockout cell line and overexpressing NEGR1 in human proximal tubular cells showed significant increases and decreases in cell migration/cell invasion, respectively. Moreover, cells deficient in NEGR1 showed no significant changes in cell migration or invasion when cells treated with rapamycin or sunitinib.
Conclusions: In summary, this study uncovered the novel role of new tumor suppressor gene that may involve in kidney tumor progression. Identifying a new TSG that contribute to RCC progression will help developing strategies to target the biological pathways that are dependent on these genes will constitute the basis for devising new therapies to treat RCC patients.