YBX2 in Cancer: From Germ Cell Gene to Oncogenic Regulator
Gene expression is controlled at numerous levels with the help of regulatory proteins. These regulatory proteins, which include transcription factors, bind to DNA and send signals that influence the rate of gene transcription by RNA. Gene regulator proteins are divided into two types: enhancers (up-regulators) and inhibitors (down-regulators), which respectively refer to proteins that lead to either an increase or decrease in the expression of a gene. Although the gene YBX2 is not the direct cause of cancer, it seems to be inextricably linked to cancer, and the latest research shows that high YBX2 expression is unfavorable in prognosis of endometrial cancer.
Overview of YBX2 Gene
YBX2 (Y-Box Binding Protein 2) is a Protein Coding gene that encodes a nucleic acid binding protein which is highly expressed in germ cells. The encoded YBX2 protein binds to a Y-box element in the promoters of certain genes but also binds to mRNA transcribed from these genes. Pseudogenes for this gene are located on chromosome 10 and 15. An important paralog of this gene is YBX3.
Protein Function
YBX2 is a germ cell-specific Y-box-binding protein. It is expressed in the germ cells of adult testes and in developing fetal testes and ovaries, but not in any other normal tissues. The function of YBX2 includes the storage and translation of mRNAs in germ cells. The YBX2 gene is expressed in early embryogenesis; however, little is known about its function. Kohno et al. reported that YBX2 is expressed in the placenta, in germ cell tumors and various human carcinomas. Its restricted pattern of expression suggests that it might be associated with cancer/testis antigens (CTAs). [2]
Diseases Associated with the YBX2 Gene
Human endometrial cancer (EC)
Human endometrial cancer (EC) is the most common gynaecological malignancy affecting women in the developed world. The exact cause of endometrial cancer is not known. An increased level of estrogen hormone may play a role, as this stimulates the buildup of the uterine lining. This may ultimately lead to abnormal overgrowth of the endometrium and cancer. Most cases of endometrial cancer occur between the ages of 60 to 70, and some cases may occur before age 40.
Izumi Suzuki et al. report data helped clarify the function of YBX2 in endometrial cancer stem cells. Endometrial cancer survival analysis plot shows YBX2 is a valuable prognostic market, with high expression being unfavorable in endometrial cancer.
Oral squamous cell carcinoma (OSCC)
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer; it involves damage to oral epithelial cells due to accumulation of multiple genetic mutations in the cells. OSCC remains a major cause of morbidity and mortality in patients with head and neck cancers. Consumption of alcohol, smoking tobacco, and chewing tobacco (with betel quid) are all potential carcinogens contributing to the high occurrence of OSCC. [4]
Xingyu Niu et al. examines the relationship among HOXA11-AS, miR-98-5p and YBX2 through the published experiments. They discovered the HOXA11-AS/miR-98-5p/YBX2 axis that provides a new therapeutic target for OSCC.
To Be Continued: Mouse Models of Ybx2
Visit the next article below, in which we provide details on the applications of mouse models used for Ybx2 gene studies and new research progress.
References
[1] https://www.genecards.org/cgi-bin/carddisp.pl?gene=YBX2
[2] Suzuki I, Yoshida S, Tabu K, Kusunoki S, Matsumura Y, Izumi H, Asanoma K, Yagi H, Onoyama I, Sonoda K, Kohno K, Taga T, Itakura A, Takeda S, Kato K. YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer. Sci Rep. 2021 Feb 18;11(1):4220. doi: 10.1038/s41598-021-83200-5. PMID: 33602962; PMCID: PMC7893073.
[3] https://www.proteinatlas.org/ENSG00000006047-YBX2/pathology/endometrial+cance
[4] Gharat SA, Momin M, Bhavsar C. Oral Squamous Cell Carcinoma: Current Treatment Strategies and Nanotechnology-Based Approaches for Prevention and Therapy. Crit Rev Ther Drug Carrier Syst. 2016;33(4):363-400. doi: 10.1615/CritRevTherDrugCarrierSyst.2016016272. PMID: 27910740.
[5] Niu X, Yang B, Liu F, Fang Q. LncRNA HOXA11-AS promotes OSCC progression by sponging miR-98-5p to upregulate YBX2 expression. Biomed Pharmacother. 2020 Jan;121:109623. doi: 10.1016/j.biopha.2019.109623. Epub 2019 Nov 12. PMID: 31731187.
