The Regulatory Effect of lncRNA PSORS1C3 on Different Variants of OCT4 in non-Pluripotent Cells

Abstract

OCT4 is the major regulator of pluripotency in embryonic stem cells and its association with tumorigenesis, cellular stress response, and homeostatic multifactorial diseases have been recently reported. To serve the versatility in its function, OCT4 generates several transcript variants which their expression levels are tightly regulated through different mechanisms. PSORS1C3 is a long non-coding RNA with overlapping genomic location with OCT4 gene. Here, we investigated the effect of PSORS1C3 overexpression on OCT4 expression in different cell lines. Our data revealed that ectopic expression of PSORS1C3 did not affect OCT4 transcripts abundance in NT2 cells, as a model of pluripotent cells. However, in HEK293T cells, PSORS1C3 overexpression led to an increase in OCT4B as a homeostatic isoform and a decrease in OCT4A transcript level. We also observed that manipulating PSORS1C3 in HeLa cells, as a model of epithelial carcinoma line, caused an upregulation in OCT4A, OCT4C which could regulate stemness and proliferation and OCT4B transcripts at different time points. Our findings indicated that PSORS1C3 could affect the expression level of OCT4 spliced variants, according to their functions and the cells molecular context as well as genetic background. Considering these diverse regulatory effects and co-expression of OCT4 and PSORS1C3 in some cell lines, it is safe to consider PSORS1C3 as a modulator of OCT4 expression in non-pluripotent cells and in association with homeostatic pathways.