MAT2B通过靶向表皮生长因子受体和增殖细胞核抗原促进骨肉瘤增殖，抑制细胞凋亡

2019年5月，上海交通大学附属第六人民医院肿瘤科(Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China) YUAN YUAN老师研究团队在《INTERNATIONAL JOURNAL OF ONCOLOGY》上发表论文：

“MAT2B promotes proliferation and inhibits apoptosis in osteosarcoma by targeting epidermal growth factor receptor and proliferating cell nuclear antigen”

“MAT2B通过靶向表皮生长因子受体和增殖细胞核抗原促进骨肉瘤增殖，抑制细胞凋亡”

Abstract：

Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young people with poor prognosis. At present, the mechanisms underlying tumorigenesis in OS are not well understood. The methionine adnosyltransferase 2B (MAT2B) gene encodes the regulatory subunit of methionine adenosyltransferase (MAT). Recent studies demonstrated that it is highly expressed in a number of human malignancies; however, is undefined in OS. In the present study, MAT2B expression was investigated in tumor samples and cell lines. In vivo and in vitro, lentivirusmediated small hairpin RNA was constructed to target the MAT2B gene and examine the role of MAT2B in OS proliferation. Microarray analysis was performed to examine the possible downstream molecular target of MAT2B in OS. MAT2B was markedly increased in OS specimens compared with the normal bone tissues, and it was additionally abundantly expressed in OS cell lines. Inhibition of MAT2B expression caused a marked decrease in proliferation and significant increase in apoptosis. In vivo, MAT2B silencing significantly inhibited OS cell growth. Microarray analysis suggested that epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) may function as downstream targets of MAT2B in OS, as confirmed by reverse transcriptionquantitative polymerase chain reaction assays and western blotting. Collectively, these results suggested that MAT2B serves a critical role in the proliferation of OS by regulating EGFR and PCNA and that it may be a potential therapeutic target and prognostic factor of OS.

摘要：

骨肉瘤(OS)是年轻人中最常见的骨肿瘤，预后较差。目前，OS中肿瘤发生的机制尚不清楚。蛋氨酸腺苷转移酶2B (MAT2B)基因编码蛋氨酸腺苷转移酶(MAT)的调控亚基。最近的研究表明，它在许多人类恶性肿瘤中高度表达;然而，在OS中未定义。在本研究中，研究人员研究了MAT2B在肿瘤样本和细胞系中的表达。在体内和体外，构建慢病毒介导的小发夹RNA，靶向MAT2B基因，研究MAT2B在OS增殖中的作用。微阵列分析检测了MAT2B在OS中可能的下游分子靶点。与正常骨组织相比，MAT2B在骨肉瘤标本中的表达明显增加，并且在骨肉瘤细胞系中也大量表达。抑制MAT2B表达导致细胞增殖明显减少，细胞凋亡明显增加。在体内，MAT2B沉默显著抑制OS细胞生长。芯片分析表明，逆转录-定量聚合酶链反应和western blotting证实，表皮生长因子受体(EGFR)和增殖细胞核抗原(PCNA)可能是OS中MAT2B的下游靶点。综上所述，这些结果表明MAT2B通过调节EGFR和PCNA在OS的增殖中起关键作用，可能是OS的潜在治疗靶点和预后因素。

该论文中，U-2O细胞、MNNG/HOS、MG-63和Saos-2细胞的体外培养是使用Ausbian特级胎牛血清完成的。欲了解或购买Ausbian特级胎牛血清可以联系北京缔一生物400-166-8600.