The Long Noncoding RNA CRNDE in HCC Induced Immune Suppression
Abstract
LncRNAs CRNDE is one of the most significantly elevated-expressed genes in HCC. CRNDE levels are reversely correlated with HCC patients prognosis. Based on our previous data, we assumed that HCC-derived CRNDE acts as inhibitory messenger molecular to impair host immunoreaction in the tumor microenvironment, and thus causing immune evasion and promoting HCC progression. During the 1st year of the performance, we evaluated the impact of CRNDE on tumor growth in vivo using a novel mouse model of HCC induced by HDTV (Hydrodynamic tail vein) injection of transposase (sleeping beauty)-based plasmids expressing YapS127A and -cateninN90. we observed that co-injecting CRNDE-expressing plasmids with YapS127A/-cateninN90 promotes HCC growth; while co-injecting shCRNDE plasmids with YapS127A/-cateninN90 attenuate Yap/-catenin-induced HCC growth. Further RNA-seq analyses of these mouse HCC tissues indicate that immune system activation level was greatly elevated in CRNDE-depleted HCC when compared with control HCC, demonstrating as higher expression of immune-response related genes; more infiltrating CD8 Tcells,CD4 memory T-cells and NK cells in tumor; and higher level of CD8 T-cells activationin tumor tissues. Next, in order to determine the effect of CRNDE on TILs functions, we carried out granzyme B ELISPOT assays using mouse TILs, which were isolated from mouse HCCs induced by HDTV injection of YapS127A/-cateninN90 in combination with CRNDE over-expression orshCRNDE plasmids and their respective control plasmids. Our data demonstrated that HCCs with CRNDE over-expression/depletion have much less/more granzyme B-secreting TILs than their corresponding control HCCs respectively. These results further support our initial assumption that the immune responses of TILs are suppressed by CRNDE in HCC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1117720
Entities
People
- Jinqiang Zhang
Organizations
- Tulane University of Louisiana