Open AccessLINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation
Author(s) -
Gong Chen,
Yuenan Liu,
Lilong Liu,
Hailong Ruan,
Qi Cao,
Zhengshuai Song,
Lin Bao,
Tianbo Xu,
Xiong Zhang,
Jingchong Liu,
Di Liu,
Huageng Liang,
Guosong Jiang,
Xiong Yang,
Hongmei Yang,
Ke Chen,
Xiaoping Zhang
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.103755
Subject(s) - sunitinib , renal cell carcinoma , cancer research , medicine , stat3 , pharmacology , signal transduction , biology , microbiology and biotechnology
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.