MEIOB基因,全称为meiosis-specific with OB domains,是一种与减数分裂过程密切相关的基因。该基因编码的单链DNA结合蛋白在DNA双链断裂(DSB)修复中发挥重要作用,尤其是在减数分裂过程中,参与同源重组和交叉形成,对维持遗传稳定性和生殖细胞正常发育至关重要。MEIOB基因的表达具有组织特异性,主要在生殖细胞中表达,尤其是在睾丸和卵巢中。在非生殖细胞中,MEIOB基因的表达通常受到抑制。
MEIOB基因的突变与多种生殖系统疾病相关。例如,在非梗阻性无精子症(NOA)患者中,MEIOB基因的突变会导致减数分裂停滞和男性不育[3,5]。这些突变可能影响MEIOB蛋白的稳定性和功能,从而干扰DNA修复过程和正常的生殖细胞发育。此外,MEIOB基因的突变还与原发性卵巢功能不全(POI)相关,这是一种导致女性生育能力下降的疾病[2,4]。POI患者中,MEIOB基因的突变可能导致卵巢发育异常和卵泡损伤,进而影响生育能力。
除了与生殖系统疾病相关外,MEIOB基因还与某些癌症的发生发展有关。研究发现,MEIOB基因的表达在某些癌症细胞中上调,如三阴性乳腺癌(TNBC)。在TNBC中,MEIOB基因的表达与不良预后相关,并且其激活与同源重组缺陷(HRD)有关。HRD是DNA修复途径的一种缺陷,会导致基因不稳定性和肿瘤的发生[1]。此外,MEIOB基因的表达还受到DNA甲基化水平的调控。去甲基化药物5-Aza-2'-deoxycytidine(DAC)可以诱导MEIOB基因的表达,使其成为癌症疫苗治疗的潜在靶点[6]。
综上所述,MEIOB基因在生殖细胞发育、DNA修复和癌症发生发展中发挥重要作用。MEIOB基因的突变与多种生殖系统疾病和癌症相关,其功能失调可能导致DNA修复缺陷、遗传不稳定性以及生殖细胞发育异常。研究MEIOB基因的功能和调控机制对于深入理解生殖和癌症的生物学过程,以及开发新的诊断和治疗策略具有重要意义。
参考文献:
1. Gu, Yayun, Wang, Cheng, Zhu, Rongxuan, Liu, Xiaoan, Hu, Zhibin. . The cancer-testis gene, MEIOB, sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency. In Cancer biology & medicine, 18, 74-87. doi:10.20892/j.issn.2095-3941.2020.0071. https://pubmed.ncbi.nlm.nih.gov/33628586/
2. Wang, Yurong, Liu, Ling, Tan, Chen, He, Wen-Bin, Tan, Yue-Qiu. 2022. Novel MEIOB variants cause primary ovarian insufficiency and non-obstructive azoospermia. In Frontiers in genetics, 13, 936264. doi:10.3389/fgene.2022.936264. https://pubmed.ncbi.nlm.nih.gov/35991565/
3. Gershoni, Moran, Hauser, Ron, Barda, Shimi, Pietrokovski, Shmuel, Kleiman, Sandra E. . A new MEIOB mutation is a recurrent cause for azoospermia and testicular meiotic arrest. In Human reproduction (Oxford, England), 34, 666-671. doi:10.1093/humrep/dez016. https://pubmed.ncbi.nlm.nih.gov/30838384/
4. Okutman, Özlem, Gürbüz, Ali Sami, Salvarci, Ahmet, Muller, Jean, Viville, Stephane. 2024. Evaluation of an Updated Gene Panel as a Diagnostic Tool for Both Male and Female Infertility. In Reproductive sciences (Thousand Oaks, Calif.), 31, 2309-2317. doi:10.1007/s43032-024-01553-4. https://pubmed.ncbi.nlm.nih.gov/38664359/
5. Zhu, Xiaoyu, Hu, Kaiqin, Cheng, Huiru, Tang, Dongdong, Guo, Rui. 2023. Novel MEIOB pathogenic variants including a homozygous non-canonical splicing variant, cause meiotic arrest and human non-obstructive azoospermia. In Clinical genetics, 105, 99-105. doi:10.1111/cge.14426. https://pubmed.ncbi.nlm.nih.gov/37715646/
6. Shiohama, Yasuo, Ohtake, Junya, Ohkuri, Takayuki, Kitamura, Hidemitsu, Nishimura, Takashi. 2014. Identification of a meiosis-specific protein, MEIOB, as a novel cancer/testis antigen and its augmented expression in demethylated cancer cells. In Immunology letters, 158, 175-82. doi:10.1016/j.imlet.2014.01.004. https://pubmed.ncbi.nlm.nih.gov/24440806/