上海交通大學(xué)基礎(chǔ)醫(yī)學(xué)院王建華研究員領(lǐng)銜的課題組新近發(fā)現(xiàn),，前列腺癌中抑癌基因HIC1的啟動子（基因的一個組成部分,，控制基因表達(dá)的起始時間和表達(dá)程度）如果出現(xiàn)高度甲基化，可能導(dǎo)致其表達(dá)沉默而失去抑癌功能,。該研究論文日前發(fā)表在國際學(xué)術(shù)刊物《臨床癌癥研究》上,。專家認(rèn)為，該研究闡明了抑癌基因在調(diào)控前列腺癌發(fā)生發(fā)展中的作用機(jī)制,。
前列腺癌是男性泌尿生殖系統(tǒng)常見的惡性腫瘤之一,，其發(fā)病率和死亡率在西方國家男性惡性腫瘤中居第二位，近年來,，在我國也呈顯著上升趨勢,。上海市前列腺癌發(fā)病率已從1990年的2.6/10萬上升至2005年的16.1/l0萬,，位列男性腫瘤的第5位,。
研究人員發(fā)現(xiàn)，在前列腺癌實體腫瘤組織中抑癌基因HIC1啟動子呈現(xiàn)高度甲基化,，可能導(dǎo)致其表達(dá)沉默而失去抑癌功能,。采用5-Aza處理前列腺癌細(xì)胞系后，HIC1甲基化降低,，HIC1表達(dá)上調(diào),。在進(jìn)一步的研究中，科研人員通過體內(nèi)外實驗表明,，恢復(fù)表達(dá)HIC1可顯著降低癌細(xì)胞增殖,、侵襲,、轉(zhuǎn)移及成瘤等能力；相反,，shRNA沉默表達(dá)HIC1后,，癌細(xì)胞這些特性則被顯著增強(qiáng)。
王建華說,，該研究有助于為前列腺癌的早期診斷和治療提供新思路,。（生物谷Bioon.com）
doi: 10.1158/1078-0432.CCR-12-2888
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HIC1 modulates prostate cancer progression by epigentic modification
Jianghua Zheng1, Jinglong Wang1, Xueqing Sun1, Mingang Hao1, Tao Ding2, Dan Xiong1, Xiumin Wang1, Yu Zhu3, Gang Xiao1, Guangcun Cheng1, Meizhong Zhao4, Jian Zhang5, and Jianhua Wang1,*
Purpose: Prostate cancer (PCa) is the second leading cause of cancer deaths among men in Western counties, which has been also occurred in Chinese male with markedly increasing incidence in recent years. Although the mechanism underlying its progression still remains unclear, epigenetic modifications are important ethological parameters. Exrimental Design: The methylation status of HIC1 promoter were assayed in cell lines, tissues and plasma of PCa patients by using MSP-PCR and bisulfate sequencing (BSP). The ability of HIC1 to regulate proliferation, migration and invasion was assessed by MTT, scratch healing assay and reconstituted extracellular matrices in porous culture chambers. Tumorigenesis，metastases and bone destruction were analyzed in mice bearing PCa cells restoring HIC1 by using Xenogen IVIS with radiographic system and small-animal PET-CT images. Microarrays were searched for genes that had correlated expression with HIC1 mRNA. Results: The methylation status of 11 CpG sites within HIC1 promoter were abundantly methylated in cell lines, tissues and plasma of PCa patients compared with those of respective normal controls. Restoring HIC1 expression in PCa cells markedly inhibited proliferation, migration, and invasion and induced the apoptosis in these cells. Moreover, mice bearing PCa-restoring HIC1 cells had a marked effect on reducing tumor growth,，multiple tissue metastases and bone destruction. Notably, we also identified that the chemokine receptor CXCR7 is a direct downstream target gene of HIC1. Conclusions: These findings suggest that therapies targeting epigenetic events regulating HIC1 expression may provide a more effective strategy for PCa treatment.
