Elucidation of long non-coding RNA Snhg7 functions in T Cells

Abstract

Abstract Long non-coding RNAs (lncRNAs) have emerged as important molecules involved in a vast number of biological processes, including transcriptional, prost-transcriptional, and epigenetic regulation. The lncRNA Small Nucleolar RNA Host Gene 7 (Snhg7) has been shown to function as a competing endogenous RNA by sequestering several microRNAs (miRNAs) including miR-34a and miR-216b. Interestingly, these specific miRNAs have been shown to target GalNac transferases in many cancers. Given that O-linked glycosylation contributes to T-cell maturation, trafficking, and survival, the objective of this study was to determine the importance of Snhg7 in T cell maturation through the regulation of GALNAc transferases via miRNA sequestration. We tested the hypothesis that Snhg7 functions to sequester miR-34a and miR-216b, thereby controlling the production of Polypeptide N-acetylgalactosaminyltransferase proteins GALNT7 and GALNT1 in T cells. Our data demonstrate that siRNA knockdown of Snhg7 in T cells leads to miR-34a- and miR-216b-dependent decreases in GALNT7 and GALNT1 protein expression, respectively. Though Snhg7 knockdown has inhibited proliferation in cancer cells lines, it increased proliferation of T cells in a Jurkat cell line in a miR-34a- and miR-216- independent manner. Surprisingly, Jurkat cells produce truncated O-glycans. These data suggests that O-glycosylation contributes to Snhg7-induced cell proliferation. Taken together, our data support the hypothesis that Snhg7 influences critical processes in T cell function and should be considered in future biomarkers of disease or novel therapeutic strategies. Supported by NIH grant ES023845.