Research Paper Volume 12, Issue 17 pp 17459—17479
LINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation
- 1 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 2 Institute of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 3 Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Received: February 24, 2020 Accepted: July 6, 2020 Published: September 13, 2020
https://doi.org/10.18632/aging.103755How to Cite
Abstract
Patients with advanced renal cell carcinoma who are resistant to sunitinib currently have limited clinical options for treatment. Therefore, it is necessary to explore the biological basis of sunitinib resistance and to uncover new targets for the intervention of sunitinib resistance. In this study, we identified that LINC00160 was associated with sunitinib resistance in renal cell carcinoma. Resistant tumor cells highly expressed LINC00160 to recruit transcriptional factor TFAP2A, which bound to SAA1 promoter regions and activated its expression. On one hand, SAA1 linked to ABCB1 protein, which facilitated sunitinib cellular efflux and diminished drug accumulation. On the other hand, SAA1 stimulated JAK-STAT signaling pathways, which countered cellular survival inhibition from drug. All these regulatory networks were well organized and collaborated, thus promoting sunitinib resistance in renal cell carcinoma. LINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation, which offers an opportunity for targeted intervention and molecular therapies in the future.