来自上海交通大学基础医学院,上海中医药大学等处的研究人员针对前列腺癌展开了研究,发现前列腺癌中抑癌基因HIC1的启动子如果出现高度甲基化,就可能导致其表达沉默而失去抑癌功能,这从表观遗传学修饰的新角度,阐明抑癌基因在调控前列腺癌发生发展中的作用机制,相关成果公布在肿瘤领域国际期刊Clinical Cancer Research上。
HIC1 modulates prostate cancer progression by epigentic modification
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.