The pioneering work from Chen's lab identified Siglec-15 as novel tumor immune suppressor, while the regulatory mechanisms underlying the broad up-regulation of Siglec-15 in human cancers were obscure currently. Here we found long non-coding RNA (lncRNA) LINC00973 was higher in Siglec-15-positive clear-cell renal cell carcinoma (ccRCC), and LINC00973 positively regulated Siglec-15 expression at transcriptional level. This effect was evidently dependent on miR-7109-3p (designated as miR-7109 hereafter), and we provided evidences supporting that Siglec-15 as direct target of miR-7109. Via sponging miR-7109, LINC00973 functioned as competing endogenous RNA (ceRNA) to control cell surface abundance of Siglec-15, and consequently was involved in cancer immune suppression. We further demonstrated that LINC00973 and miR-7109 expression in ccRCC antagonistically influenced immune activation of co-cultured Jurkat cells. Our study highlighted the importance of LINC00973-miR-7109-Siglec-15 in immune evasion in ccRCC, which offered significant opportunity for both therapeutic intervention and diagnostic/prognostic exploitations.
Cancer science. 2020 Aug 11 [Epub ahead of print]
Yanbin Liu, Xingzhi Li, Changming Zhang, Hui Zhang, Yali Huang
Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China., Department of urological surgery, Longgang District People's Hospital of Shenzhen, Shenzhen, China., Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.