Open AccessLINC00973 is involved in cancer immune suppression through positive regulation of Siglec‐15 in clear‐cell renal cell carcinoma
Author(s) -
Liu Yanbin,
Li Xingzhi,
Zhang Changming,
Zhang Hui,
Huang Yali
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14611
Subject(s) - immune system , clear cell renal cell carcinoma , downregulation and upregulation , biology , cancer research , siglec , jurkat cells , competing endogenous rna , cell , renal cell carcinoma , immunology , t cell , long non coding rna , medicine , gene , genetics
The pioneering work from Lieping Chen’s laboratory identified Siglec‐15 as a novel tumor immune suppressor, while the regulatory mechanisms underlying the broad upregulation of Siglec‐15 in human cancers remain obscure. Here we found that 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 evidence that Siglec‐15 is a direct target of miR‐7109. Through 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 offers significant opportunity for both therapeutic intervention and diagnostic/prognostic exploitations.