Long Noncoding RNA <i>KIF9-AS1</i> Regulates Transforming Growth Factor-β and Autophagy Signaling to Enhance Renal Cell Carcinoma Chemoresistance via microRNA-497-5p
Yichen Jin, Ru Huang, Yanfu Xia, Chen Huang, Feng Qiu, Jinxian Pu, Xuefeng He, Xiaojun Zhao
Abstract
Renal cell carcinoma (RCC) has been regarded as one of the most malignant tumor types. Chemotherapy (such as sorafenib) is used as common strategy for treating RCC. To date, whether long noncoding RNA KIF9-AS1 is involved in RCC progression and drug resistance remains unknown. In this investigation, we detected gene expression levels by western blot and RT-qPCR. MTT and TUNEL experiments were used to show cell viability and apoptosis, respectively. KIF9-AS1 overexpression led to enhanced cell viability, increased IC50 value of sorafenib, and decreased apoptosis. miR-497-5p acted as key interaction factor for KIF9-AS1 in RCC. More importantly, we found that transforming growth factor-β and autophagy signaling pathways were both critical effectors for mediating KIF9-AS1/miR-497-5p axis-induced drug resistance phenotypes (cell viability, IC50, apoptosis) of RCC. In conclusion, our study revealed that KIF9-AS1 played a positive role in drug resistance of RCC cells to sorafenib, potentially driving the development of targeted diagnostic and therapeutical approaches.