lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells

Abstract

OCT4 is a transcription factor known for its regulatory roles in stemness, tumorigenesis and stress response. Considering its versatile functions, expression of OCT4 is regulated at different levels. PSORS1C3, a long non-coding RNA overlapped with OCT4, has a putative association with immune mediated diseases; however, its exact functions remained to be elucidated. Here, we demonstrated that PSORS1C3 is regulated by glucocorticoids (GC), has two endogenously active promoters, promoter 0 and 1, and two sets of transcripts, short and long variants. According to our findings, PSORS1C3 promoters behaved differently during neural differentiation of NT2 cells and glucocorticoid receptor (GR) activation. In both processes the expression pattern of short variants differed from that of long variants and was similar to OCT4 expression. Furthermore, our data revealed that PSORS1C3’s promoter 0 could act as an enhancer for OCT4 in non-pluripotent cells, where its deletion caused a significant decrease in OCT4 expression. Meanwhile, during GR activation promoter 0 functioned as a negative regulator and alleviated transcription induction of OCT4 after GC treatment. Altogether, our work clarified the structure and regulation of PSORS1C3, explained its relation to immune-related disease through GR signaling and introduced it as a novel fine-tuner of OCT4 expression in non-pluripotent cells.

Expression and Function of C1orf132 Long-Noncoding RNA in Breast Cancer Cell Lines and Tissues

“…Our in-silico studies revealed two potential promoters in addition to the previously known miRNAs precursor promoter [12], as well as two groups of long and short transcripts for C1orf132. The reason for generating short and long transcripts of the gene is not known, however, we observed a similar pattern of short and long transcripts for PSORS1C3 lncRNA in our previous study [17]. There is a possibility that this kind of gene expression regulation by alternative splicing in a tissue-and cell-specific manner is a more general feature of lncRNAs, and their possible dysregulation could contribute to pathogenesis of many cancers [18].…”

Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models

“…However, it is unclear which of these are responsible for its therapeutic effect. Studies have suggested that non-coding RNAs, such as miRNAs and lncRNAs, could inhibit inflammatory diseases (Stagakis et al, 2011;Liu et al, 2020) and MP has been shown to regulate the expression of non-coding RNAs to inhibit specific proinflammatory targets (Davis et al, 2013;Mirzadeh et al, 2019).…”

Linking long noncoding RNAs (lncRNAs) and doping detection

“…Similarly, Perry et al 34 investigated lncRNA expression after dexamethasone treatment of primary airway smooth muscle cells and verified a dramatic change in their expression profile, with 27 lncRNAs increased and 39 decreased after treatment. Moreover, dexamethasone regulates the expression of PSORS1C3, a psoriasis‐related lncRNA 35 . In an animal model, T cells from mice treated with Δ9‐tetrahydrocannabinol (THC) showed differential expression of several lncRNAs 36 .…”