Long Noncoding RNA SOX2-OT: Regulations, Functions, and Roles on Mental Illnesses, Cancers, and Diabetic Complications

Abstract

SRY-box transcription factor 2 (SOX2) overlapping transcript (SOX2-OT) is an evolutionarily conserved long noncoding RNA. Its intronic region contains the SOX2 gene, the major regulator of the pluripotency of embryonic stem cells. The human SOX2-OT gene comprises multiple exons and has multiple transcription start sites and generates hundreds of transcripts. Transcription factors (IRF4, AR, and SOX3), transcriptional inhibitors (NSPc1, MTA3, and YY1), and miRNAs (miR-211 and miR-375) have been demonstrated to control certain SOX2-OT transcript level at the transcriptional or posttranscriptional levels. Accumulated evidence indicates its crucial roles in the regulation of the SOX2 gene, miRNAs, and transcriptional process. Restricted expression of SOX2-OT transcripts in the brain results in the association between SOX2-OT single nucleotide polymorphisms and mental illnesses such as schizophrenia and anorexia nervosa. SOX2-OT is notably elevated in tumor tissues, and a high level of SOX2-OT is well correlated with poor clinical outcomes in cancer patients, leading to the establishment of its role as an oncogene and a prognostic or diagnostic biomarker for cancers. The emerging evidence supports that SOX2-OT mediates diabetic complications. In summary, SOX2-OT has diversified functions and could be a therapeutic target for various diseases.

Expression of SOX2OT, DANCR and TINCR long non‑coding RNAs in papillary thyroid cancer and its effects on clinicopathological features

“…Some studies have indicated that SOX2OT lncRNA contributes to tumorigenesis via different mechanisms ( 11 , 31 ). For example, it regulates the expression of the SOX2 gene, which is located in its intronic region and has a key role in regulating the pluripotency properties of embryonic stem cells ( 32 ).…”

“…In a number of studies, it has been reported that it regulates the expression of genes involved in tumorigenesis, especially by binding to tumor suppressor miRNAs ( 12 , 14 , 33 ). Li et al ( 11 ) reported that SOX2OT interacts with epigenetic regulators or directly binds to the transcription factors and destabilizes them. Studies have revealed that SOX2OT is an oncogene and its expression increases in esophageal squamous cell, bladder, nasopharyngeal, prostate, non-small-cell lung, gastric and hepatocellular cancer alongside glioma ( 10 , 11 ).…”

“…This gene serves a key role in maintaining both pluripotency and self-renewal properties of embryonic stem cells (9,10). Many studies have revealed that the increase in SOX2OT expression in cancer cells induces SOX2 expression and this in turn contributes to tumorigenesis (11)(12)(13)(14). The changes in SOX2OT expression have been associated with a number of cancers such as lung, breast, esophageal, gastric, hepatocellular and ovarian (10).…”

Long non-coding RNA-associated competing endogenous RNA axes in the olfactory epithelium in schizophrenia: a bioinformatics analysis

“…According to genome-wide association studies (GWAS), there are associations between mental disorders (e.g., general cognitive disorders, SCZ, eating disorders, insomnia, anorexia nervosa, and night sleep phenotypes) and SOX-OT -mapped single nucleotide polymorphisms (SNPs). Mental conditions account for over half of SOX2-OT -related disorders 44 . FLG-AS1 and AQP4-AS1 are two other DElncRNAs that were identified by our analysis.…”

The Roles of Noncoding RNAs in the Development of Osteosarcoma Stem Cells and Potential Therapeutic Targets

“…LncRNA SOX2-OT has been characterized as an oncogene and is highly expressed in various cancers ( Li PY. et al, 2020 ).…”