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
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]
Figure 1. AlphaFold structure prediction (YBX2) (Source: Uniprot)
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.
Figure 2. Endometrial cancer survival analysis plot [3]
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.
Figure 3. YBX2 level was regulated by HOXA11-AS and miR-98-5p [5]
HOXA11-AS was highly expressed in OSCC tissues and cells. Knockdown of HOXA11-AS significantly reduced proliferation, migration, invasion and EMT, while promoting apoptosis of OSCC cells. MiR-98-5p was a target of HOXA11-AS, and its inhibitor could revert the inhibition effect of silenced-HOXA11-AS on the progression of OSCC. Also, YBX2 was a target of miR-98-5p, and its overexpression could invert the suppression effect of miR-98-5p overexpression on the progression of OSCC. YBX2 expression was regulated by HOXA11-AS and miR-98-5p. Furthermore, HOXA11-AS silencing could reduce the tumor growth of OSCC in vivo.[5]
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.
>>Learn more: Ybx2 Mice 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+cancer
[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.
