近日,，國際腫瘤學(xué)領(lǐng)域著名雜志Oncogene刊登了中山大學(xué)醫(yī)學(xué)院研究人員的最新研究結(jié)果“MiR-135a functions as a selective killer of malignant glioma。”,，研究人員報(bào)道了在惡性膠質(zhì)瘤的分子靶向治療基礎(chǔ)研究方面的一項(xiàng)重要進(jìn)展,。這項(xiàng)研究由中山大學(xué)副校長顏光美領(lǐng)導(dǎo)其研究組完成,，第一作者是中山大學(xué)生命科學(xué)學(xué)院直博生吳思涵，這項(xiàng)研究工作自吳思涵二年級(jí)時(shí)已經(jīng)全部完成,。
該研究成果闡述了一種在神經(jīng)膠質(zhì)細(xì)胞高豐度表達(dá)的小分子RNA miR-135a對惡性膠質(zhì)瘤具有選擇性殺傷作用,。該分子在惡性膠質(zhì)瘤中低表達(dá)，并與臨床病理分級(jí)呈負(fù)相關(guān)關(guān)系，提示miR-135a的缺失可能參與了膠質(zhì)瘤的發(fā)生發(fā)展,。該研究還發(fā)現(xiàn),，miR-135a能選擇性誘導(dǎo)惡性膠質(zhì)瘤發(fā)生線粒體通路依賴性的凋亡，而不殺傷正常的膠質(zhì)細(xì)胞和神經(jīng)元,。應(yīng)用膠質(zhì)瘤的動(dòng)物模型進(jìn)一步證實(shí)了miR-135a對惡性膠質(zhì)瘤的成瘤,、生長的抑制作用以及對模型動(dòng)物生存期的延長效應(yīng)。
惡性膠質(zhì)瘤是中樞神經(jīng)系統(tǒng)最常見的惡性腫瘤,，即使采取綜合治療方案,，患者的五年生存率仍低于5.5％。當(dāng)今膠質(zhì)瘤治療的研究重點(diǎn)是：探索膠質(zhì)瘤發(fā)生發(fā)展的分子機(jī)制和尋求更加具有特異性的治療靶點(diǎn),。
據(jù)顏光美教授介紹,，吳思涵是來自中山大學(xué)生命科學(xué)學(xué)院的直博生，該項(xiàng)研究工作在吳思涵二年級(jí)時(shí)已經(jīng)全部完成,。這一成果不僅有助于我們更深入地了解惡性膠質(zhì)瘤的發(fā)生發(fā)展過程中誘導(dǎo)癌細(xì)胞惡性表型的關(guān)鍵因子和信號(hào)通路,，而且有望為臨床惡性膠質(zhì)瘤的基因靶向治療提供新的靶點(diǎn)，具有較好的轉(zhuǎn)化醫(yī)學(xué)研究前景,。（生物谷Bioon.com）
doi:10.1038/onc.2011.551
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MiR-135a functions as a selective killer of malignant glioma.
Wu S, Lin Y, Xu D, Chen J, Shu M, Zhou Y, Zhu W, Su X, Zhou Y, Qiu P, Yan G.
Glioma is the most common and fatal primary brain tumor. Thus far, therapeutic strategies to efficiently and specifically antagonize glioma are limited and poorly developed. Here we report that glia-enriched miR-135a, a microRNA that is dramatically downregulated in malignant glioma and correlated with the pathological grading, is capable of inducing mitochondria-dependent apoptosis of malignant glioma by regulating various genes including STAT6, SMAD5 and BMPR2, as well as affecting the signaling pathway downstream. Moreover, this lethal effect is selectively towards malignant glioma cells, but not neurons and glial cells, through a novel mechanism. Our findings suggest an important role of miR-135a in glioma etiology and provide a potential candidate for malignant glioma therapy.
