MAT2B通過靶向表皮生長因子受體和增殖細胞核抗原促進骨肉瘤增殖，抑制細胞凋亡

2019年5月，上海交通大學附屬第六人民醫院腫瘤科(Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China) YUAN YUAN老師研究團隊在《INTERNATIONAL JOURNAL OF ONCOLOGY》上發表論文：

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

“MAT2B通過靶向表皮生長因子受體和增殖細胞核抗原促進骨肉瘤增殖，抑制細胞凋亡”

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)是年輕人中最常見的骨腫瘤，預后較差。目前，OS中腫瘤發生的機制尚不清楚。蛋氨酸腺苷轉移酶2B (MAT2B)基因編碼蛋氨酸腺苷轉移酶(MAT)的調控亞基。最近的研究表明，它在許多人類惡性腫瘤中高度表達;然而，在OS中未定義。在本研究中，研究人員研究了MAT2B在腫瘤樣本和細胞系中的表達。在體內和體外，構建慢病毒介導的小發夾RNA，靶向MAT2B基因，研究MAT2B在OS增殖中的作用。微陣列分析檢測了MAT2B在OS中可能的下游分子靶點。與正常骨組織相比，MAT2B在骨肉瘤標本中的表達明顯增加，并且在骨肉瘤細胞系中也大量表達。抑制MAT2B表達導致細胞增殖明顯減少，細胞凋亡明顯增加。在體內，MAT2B沉默顯著抑制OS細胞生長。芯片分析表明，逆轉錄-定量聚合酶鏈反應和western blotting證實，表皮生長因子受體(EGFR)和增殖細胞核抗原(PCNA)可能是OS中MAT2B的下游靶點。綜上所述，這些結果表明MAT2B通過調節EGFR和PCNA在OS的增殖中起關鍵作用，可能是OS的潛在治療靶點和預后因素。

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