Inactivation of tumor suppressor gene HIC1 in gastric cancer is reversed via small activating RNAs

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• 作者：Shengli Pan ; Zhiwei Wang ; Yinan Chen ; Xuehua Chen ; Jun Ji ; Jianian Zhang ; Jianfang Li ; Qu Cai ; Bingya Liu ; Zhenggang Zhu ; Yingyan Yu
• 关键词：HIC1 ; hypermethylated in cancer 1 ; dsRNA ; double-stranded RNA ; SNP ; Single nucleotide polymorphism ; RNAa ; RNA-induced gene activation ; RNAi ; RNA interference
• 刊名：Gene
• 出版年：2013
• 出版时间：15 September, 2013
• 年：2013
• 卷：527
• 期：1
• 页码：102-108
• 全文大小：1392 K

文摘

HIC1 is a tumor suppressor gene that is down-expressed in different malignancies, in part, because of promoter hypermethylation. However, the biological function of HIC1 in gastric cancer remains unclear. It is known that small double-stranded RNAs can induce gene expression by targeting promoter sequences. In the present study, we examined the expression levels of HIC1 in gastric cancer tissue. Several pieces of small double-stranded RNAs were used for the activation of HIC1. Tissue microarray analysis of gastric cancer indicated that down-regulation of HIC1 in gastric cancer tissue was dramatic compared with the adjacent gastric mucosa. Gastric cancer cell lines also showed down-regulated HIC1 expression compared with a human immortalized gastric mucosa cell line. One out of four dsRNAs produced activation of HIC1 as assessed by real-time PCR and Western blotting. Use of a cell counting kit 8 and clonogenicity assays indicated that dsRNA-mediated re-expression of HIC1 inhibited cell proliferation and clonogenicity in gastric cancer. Reactivation of HIC1 suppressed cell migration and induced cell cycle arrest in the G0/G1 phase, as well as induced apoptosis. These results suggest that HIC1 is a potential target of gene therapy against gastric cancer, and that dsRNAs could function as a therapeutic option for up-regulating tumor suppressor genes in gastric cancer and other malignancies.