MAT2B通過(guò)靶向表皮生長(zhǎng)因子受體和增殖細(xì)胞核抗原促進(jìn)骨肉瘤增殖，抑制細(xì)胞凋亡

2019年5月，上海交通大學(xué)附屬第六人民醫(yī)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(tuán)隊(duì)在《INTERNATIONAL JOURNAL OF ONCOLOGY》上發(fā)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(guò)靶向表皮生長(zhǎng)因子受體和增殖細(xì)胞核抗原促進(jìn)骨肉瘤增殖，抑制細(xì)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(jiàn)的骨腫瘤，預(yù)后較差。目前，OS中腫瘤發(fā)生的機(jī)制尚不清楚。蛋氨酸腺苷轉(zhuǎn)移酶2B (MAT2B)基因編碼蛋氨酸腺苷轉(zhuǎn)移酶(MAT)的調(diào)控亞基。最近的研究表明，它在許多人類(lèi)惡性腫瘤中高度表達(dá);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(xì)胞系中的表達(dá)。在體內(nèi)和體外，構(gòu)建慢病毒介導(dǎo)的小發(fā)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(cè)了MAT2B在OS中可能的下游分子靶點(diǎn)。與正常骨組織相比，MAT2B在骨肉瘤標(biāo)本中的表達(dá)明顯增加，并且在骨肉瘤細(xì)胞系中也大量表達(dá)。抑制MAT2B表達(dá)導(dǎo)致細(xì)胞增殖明顯減少，細(xì)胞凋亡明顯增加。在體內(nèi)，MAT2B沉默顯著抑制OS細(xì)胞生長(zhǎng)。芯片分析表明，逆轉(zhuǎn)錄-定量聚合酶鏈反應(yīng)和western blotting證實(shí)，表皮生長(zhǎng)因子受體(EGFR)和增殖細(xì)胞核抗原(PCNA)可能是OS中MAT2B的下游靶點(diǎn)。綜上所述，這些結(jié)果表明MAT2B通過(guò)調(diào)節(jié)EGFR和PCNA在OS的增殖中起關(guān)鍵作用，可能是OS的潛在治療靶點(diǎn)和預(yù)后因素。

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