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提示1表达抑制人SGC7901胃癌细胞的增殖并促进其放射敏感性。

Hint1 expression inhibits proliferation and promotes radiosensitivity of human SGC7901 gastric cancer cells.

作者信息

Wei Xiaowei, Zhou Jin, Hong Lingzhi, Xu Zhi, Zhao Huanyu, Wu Xiaomin, Chen Jinfei

机构信息

Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.

Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.

出版信息

Oncol Lett. 2018 Aug;16(2):2135-2142. doi: 10.3892/ol.2018.8900. Epub 2018 Jun 5.

Abstract

Gastric cancer is a prevalent, malignant tumor that frequently escapes treatment. Histidine triad nucleotide-binding protein 1 (Hint1) is a haploinsufficient tumor suppressor gene which contributes to intercellular communication, helps to regulate cell proliferation and survival, and is frequently underexpressed in gastric cancer. To examine the involvement of Hint1 in gastric cancer, small interfering RNA was used to knock down Hint1 expression in the human gastric cancer cell line SGC-7901. The data revealed that Hint1 inhibited cell proliferation, reduced radiation-induced DNA damage repair and caused G1 phase arrest, which increased the radiosensitivity of gastric cancer cells. Further mechanistic studies revealed a novel function of Hint1, whereby it acted as a negative regulator of extracellular signal-regulated kinase. These results demonstrated the critical function of Hint1 in the biology of human gastric cancer. Acting as a tumor growth suppressor and a radiosensitive agent, this protein is a potential biomarker and may be an attractive target for specific therapeutic interventions against gastric cancer.

摘要

胃癌是一种常见的恶性肿瘤,常常难以治疗。组氨酸三联体核苷酸结合蛋白1(Hint1)是一种单倍体不足的肿瘤抑制基因,它有助于细胞间通讯,调节细胞增殖和存活,且在胃癌中常常表达不足。为了研究Hint1在胃癌中的作用,使用小干扰RNA敲低人胃癌细胞系SGC-7901中Hint1的表达。数据显示,Hint1抑制细胞增殖,减少辐射诱导的DNA损伤修复并导致G1期阻滞,从而增加胃癌细胞的放射敏感性。进一步的机制研究揭示了Hint1的一种新功能,即它作为细胞外信号调节激酶的负调节因子发挥作用。这些结果证明了Hint1在人类胃癌生物学中的关键作用。作为一种肿瘤生长抑制剂和放射敏感剂,这种蛋白是一种潜在的生物标志物,可能是针对胃癌的特异性治疗干预的有吸引力的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b30/6036515/dcac8de74ddc/ol-16-02-2135-g00.jpg

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