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

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2020 Dec 9

PMID 33294436

Citations 15

Authors

Pu-Yu Li

Ping Wang

She-Gan Gao

Dao-Yin Dong

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Endo C, Johnson T, Morino R, Nakazono K, Kamitsuji S, Akita M . Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations. Sci Rep. 2018; 8(1):8974. PMC: 5997657. DOI: 10.1038/s41598-018-27145-2. View

Su R, Cao S, Ma J, Liu Y, Liu X, Zheng J . Knockdown of SOX2OT inhibits the malignant biological behaviors of glioblastoma stem cells via up-regulating the expression of miR-194-5p and miR-122. Mol Cancer. 2017; 16(1):171. PMC: 5683208. DOI: 10.1186/s12943-017-0737-1. View

Zhan Y, Chen Z, He S, Gong Y, He A, Li Y . Long non-coding RNA SOX2OT promotes the stemness phenotype of bladder cancer cells by modulating SOX2. Mol Cancer. 2020; 19(1):25. PMC: 6998848. DOI: 10.1186/s12943-020-1143-7. View

Tian W, Jiang C, Huang Z, Xu D, Zheng S . Comprehensive analysis of dysregulated lncRNAs, miRNAs and mRNAs with associated ceRNA network in esophageal squamous cell carcinoma. Gene. 2019; 696:206-218. DOI: 10.1016/j.gene.2019.02.051. View

Zhang Y, Chang B, Zhang J, Wu X . LncRNA SOX2OT alleviates the high glucose-induced podocytes injury through autophagy induction by the miR-9/SIRT1 axis. Exp Mol Pathol. 2019; 110:104283. DOI: 10.1016/j.yexmp.2019.104283. View

Chen L, Zhang J, Chen Q, Ge W, Meng L, Huang X . Long noncoding RNA SOX2OT promotes the proliferation of pancreatic cancer by binding to FUS. Int J Cancer. 2019; 147(1):175-188. DOI: 10.1002/ijc.32827. View

Arisi I, DOnofrio M, Brandi R, Felsani A, Capsoni S, Drovandi G . Gene expression biomarkers in the brain of a mouse model for Alzheimer's disease: mining of microarray data by logic classification and feature selection. J Alzheimers Dis. 2011; 24(4):721-38. DOI: 10.3233/JAD-2011-101881. View

Song X, Yao H, Liu J, Wang Q . The prognostic value of long noncoding RNA Sox2ot expression in various cancers: A systematic review and meta-analysis. Clin Chim Acta. 2018; 484:52-59. DOI: 10.1016/j.cca.2018.05.038. View

Fenoglio C, Oldoni E, Serpente M, De Riz M, Arcaro M, DAnca M . LncRNAs expression profile in peripheral blood mononuclear cells from multiple sclerosis patients. J Neuroimmunol. 2018; 324:129-135. DOI: 10.1016/j.jneuroim.2018.08.008. View

10.

Teng Y, Kang H, Chu Y . Identification of an Exosomal Long Noncoding RNA SOX2-OT in Plasma as a Promising Biomarker for Lung Squamous Cell Carcinoma. Genet Test Mol Biomarkers. 2019; 23(4):235-240. DOI: 10.1089/gtmb.2018.0103. View

11.

Qu F, Cao P . Long noncoding RNA SOX2OT contributes to gastric cancer progression by sponging miR-194-5p from AKT2. Exp Cell Res. 2018; 369(2):187-196. DOI: 10.1016/j.yexcr.2018.05.017. View

12.

Wei R, Ding C, Alarcon Rodriguez R, Mullor M . The SOX2OT/miR-194-5p axis regulates cell proliferation and mobility of gastric cancer through suppressing epithelial-mesenchymal transition. Oncol Lett. 2018; 16(5):6361-6368. PMC: 6202518. DOI: 10.3892/ol.2018.9433. View

13.

Boraska V, Franklin C, Floyd J, Thornton L, Huckins L, Southam L . A genome-wide association study of anorexia nervosa. Mol Psychiatry. 2014; 19(10):1085-94. PMC: 4325090. DOI: 10.1038/mp.2013.187. View

14.

Li Z, Li J, Ji D, Leng K, Xu Y, Huang L . Overexpressed long noncoding RNA Sox2ot predicts poor prognosis for cholangiocarcinoma and promotes cell proliferation and invasion. Gene. 2017; 645:131-136. DOI: 10.1016/j.gene.2017.12.017. View

15.

Goes F, McGrath J, Avramopoulos D, Wolyniec P, Pirooznia M, Ruczinski I . Genome-wide association study of schizophrenia in Ashkenazi Jews. Am J Med Genet B Neuropsychiatr Genet. 2015; 168(8):649-59. DOI: 10.1002/ajmg.b.32349. View

16.

Fang Z, Che D, Qing S, Li Q, Men H, Yuan L . The lncRNA SOX2OT rs9839776 C>T Polymorphism Indicates Recurrent Miscarriage Susceptibility in a Southern Chinese Population. Mediators Inflamm. 2019; 2019:9684703. PMC: 6885167. DOI: 10.1155/2019/9684703. View

17.

Li Z, Jiang P, Li J, Peng M, Zhao X, Zhang X . Tumor-derived exosomal lnc-Sox2ot promotes EMT and stemness by acting as a ceRNA in pancreatic ductal adenocarcinoma. Oncogene. 2018; 37(28):3822-3838. DOI: 10.1038/s41388-018-0237-9. View

18.

Farhangian P, Jahandoost S, Mowla S, Khalili M . Differential expression of long non-coding RNA SOX2OT in gastric adenocarcinoma. Cancer Biomark. 2018; 23(2):221-225. DOI: 10.3233/CBM-181325. View

19.

Shafiee M, Aleyasin S, Mowla S, Vasei M, Yazdanparast S . The Effect of MicroRNA-375 Overexpression, an Inhibitor of -Induced Carcinogenesis, on lncRNA SOX2OT. Jundishapur J Microbiol. 2016; 9(9):e23464. PMC: 5081003. DOI: 10.5812/jjm.23464. View

20.

Shalem O, Sanjana N, Hartenian E, Shi X, Scott D, Mikkelson T . Genome-scale CRISPR-Cas9 knockout screening in human cells. Science. 2013; 343(6166):84-87. PMC: 4089965. DOI: 10.1126/science.1247005. View