HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation.
HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation.
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DOI：
10.3389/fonc.2020.01667
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发表时间：
2020
影响因子：
4.7
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Song Y;Tu J;Cheng Y;Zhou F;Liu P;Zhou S;Gu Y;Sun Y
HHIP是Hedgehog信号通路的负调控蛋白，在胃癌等多种肿瘤中表达异常。然而，HHIP在胃癌中的抑制作用以及HHIP调控的分子机制尚未完全阐明。在这项研究中，我们证明HHIP过表达显着抑制AGS细胞的增殖和侵袭3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物（MTT）和transwell测定，分别评估。有趣的是，甲基化特异性聚合酶链反应（MS-PCR，MSP）显示HHIP过表达显着降低其在AGS细胞中的从头启动子甲基化水平。此外，HHIP在癌旁非癌组织中的表达高于匹配的胃癌组织。高HHIP水平与转移呈负相关（p = 0.035），但与局部复发无关（p = 0.58）。综上所述，我们的研究表明，HHIP可以通过反馈方式调节其从头启动子甲基化水平来调节胃癌的进展和转移。低水平HHIP表达与胃癌转移呈正相关，提示HHIP可作为胃癌的保护性标志物，恢复HHIP表达可能是临床治疗的一种潜在策略。
Human hedgehog-interacting protein (HHIP), a negative regulator of hedgehog (HH) signaling pathway, has been reported to be dysregulated in many types of cancer, including gastric cancer. However, the inhibitory role of HHIP as well as the underlying molecular mechanism of HHIP regulation in gastric cancer haven’t been fully elucidated yet. In this study, we demonstrated that HHIP overexpression significantly suppressed the proliferation and invasion of AGS cells evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays, respectively. Interestingly, methylation-specific polymerase chain reaction (MS-PCR, MSP) showed that HHIP overexpression dramatically decreased its de novo promoter methylation levels in AGS cells. Furthermore, HHIP expression was higher in adjacent non-cancerous tissue compared to matched gastric cancer tissue. High HHIP level was negatively correlated with metastasis (p = 0.035) but not local recurrence (p = 0.58). Taken together, our study suggested that HHIP can modulate gastric cancer progression and metastasis via regulation of its de novo promoter methylation levels in a feedback manner. Lower HHIP levels is positively associated with gastric cancer metastasis, which not only indicates HHIP could be served as a protective marker for gastric cancer, but also suggests restoring HHIP expression might be a potential therapeutic strategy for clinical treatment.
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影响因子：
--
作者：
Akyala AI;Peppelenbosch MP
通讯作者：
Peppelenbosch MP
DOI：
10.2147/copd.s213519
发表时间：
2019-01-01
影响因子：
2.8
作者：
Bartholo, Thiago Prudente;Porto, Luis Cristovio;Da Costa, Claudia Henrique
通讯作者：
Da Costa, Claudia Henrique
影响因子：
11.4
作者：
Milone MC;O'Doherty U
通讯作者：
O'Doherty U
影响因子：
3.7
作者：
Zhao, Jian-Guo;Wang, Jian-Fang;Ye, Wan-Li
通讯作者：
Ye, Wan-Li
影响因子：
16.6
作者：
Kwong, Lina;Bijlsma, Maarten F.;Roelink, Henk
通讯作者：
Roelink, Henk