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粒头样蛋白 2 在胃癌中的表达及作用。

Expression and role of grainyhead-like 2 in gastric cancer.

机构信息

Department of Gastrointestinal Surgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

出版信息

Med Oncol. 2013 Dec;30(4):714. doi: 10.1007/s12032-013-0714-5. Epub 2013 Sep 26.

DOI:10.1007/s12032-013-0714-5
PMID:24068586
Abstract

The aim of this study was to evaluate the expression and role of Grhl2 in gastric cancer. Immunohistochemistry was performed to explore the expression of Grhl2 in gastric cancer and surrounding non-tumor tissues. Moreover, the mRNA and protein expression level of Grhl2 in human immortalized gastric epithelial cell line GES-1 and four gastric cancer cell lines (MGC803, SGC7901, MKN45, HGC27) were detected by qRT-PCR and Western blotting, respectively. To further investigate the role of Grhl2 in gastric cancer as well as the potential mechanisms, SGC7901 cells were transfected with lentiviral constructs expressing Grhl2 or empty vector, and then proliferation and apoptosis of SGC7901 cells were evaluated by MTT assay and flow cytometry, respectively. Finally, the protein expression level of c-Myc and Bcl-2 was detected by Western blotting. Both mRNA and protein expression level of Grhl2 were significantly downregulated in gastric cancer. Exogenous Grhl2 transduced into SGC7901 cells significantly inhibited the proliferation and promoted apoptosis. Meanwhile, over-expression of Grhl2 decreased c-Myc and Bcl-2 protein expression level. Taken together, our results demonstrated that Grhl2 downregulated in gastric cancer and may function as a tumor suppressor and play an important role in the development and progression of gastric cancer. These results may provide a new clue for treatment for gastric cancer.

摘要

本研究旨在评估 Grhl2 在胃癌中的表达和作用。通过免疫组织化学方法探讨 Grhl2 在胃癌及周围非肿瘤组织中的表达。此外,通过 qRT-PCR 和 Western blot 分别检测人永生化胃上皮细胞系 GES-1 和四种胃癌细胞系(MGC803、SGC7901、MKN45、HGC27)中 Grhl2 的 mRNA 和蛋白表达水平。为了进一步研究 Grhl2 在胃癌中的作用及其潜在机制,将慢病毒构建体表达 Grhl2 或空载转染 SGC7901 细胞,然后通过 MTT assay 和流式细胞术分别评估 SGC7901 细胞的增殖和凋亡。最后,通过 Western blot 检测 c-Myc 和 Bcl-2 的蛋白表达水平。Grhl2 的 mRNA 和蛋白表达水平在胃癌中均显著下调。外源性 Grhl2 转染 SGC7901 细胞后显著抑制增殖并促进凋亡。同时,Grhl2 的过表达降低了 c-Myc 和 Bcl-2 蛋白的表达水平。综上所述,我们的研究结果表明,Grhl2 在胃癌中下调,可能作为一种肿瘤抑制因子,在胃癌的发生和发展中发挥重要作用。这些结果可能为胃癌的治疗提供新的线索。

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本文引用的文献

1
Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium.[corrected].证据表明粒头样蛋白 2 在人类黏液纤毛气道上皮的建立和维持中具有多种作用。[已更正]
Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9356-61. doi: 10.1073/pnas.1307589110. Epub 2013 May 20.
2
Correction: grhl2 determines the epithelial phenotype of breast cancers and promotes tumor progression.更正:grhl2决定乳腺癌的上皮表型并促进肿瘤进展。
PLoS One. 2013 Apr 8;8(4). doi: 10.1371/annotation/aa633603-370b-4613-bf35-2e5f999cff38. Print 2013.
3
Bridging cancer biology with the clinic: relative expression of a GRHL2-mediated gene-set pair predicts breast cancer metastasis.
GRHL2表达在乳腺癌侵袭性中发挥作用,并可作为乳腺癌的预后和诊断生物标志物。
Clin Med Insights Oncol. 2022 Jul 21;16:11795549221109511. doi: 10.1177/11795549221109511. eCollection 2022.
4
Abnormal GRHL2 Methylation Confers Malignant Progression to Acute Leukemia.异常的GRHL2甲基化赋予急性白血病恶性进展能力。
Appl Bionics Biomech. 2022 Jul 9;2022:9708829. doi: 10.1155/2022/9708829. eCollection 2022.
5
Grainyhead-like (Grhl) Target Genes in Development and Cancer.粒头样 (Grhl) 靶基因在发育和癌症中的作用。
Int J Mol Sci. 2022 Mar 1;23(5):2735. doi: 10.3390/ijms23052735.
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Integrative omics analysis reveals effective stratification and potential prognosis markers of pan-gastrointestinal cancers.整合组学分析揭示了泛胃肠道癌症的有效分层及潜在预后标志物。
iScience. 2021 Jul 8;24(8):102824. doi: 10.1016/j.isci.2021.102824. eCollection 2021 Aug 20.
7
Grainyhead-Like Genes Family May Act as Novel Biomarkers in Colon Cancer.颗粒头样基因家族可能作为结肠癌的新型生物标志物。
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将癌症生物学与临床联系起来:GRHL2 介导的基因对的相对表达可预测乳腺癌转移。
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8
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9
Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis.靶向肿瘤抑制因子 GRHL3 的 miR-21 依赖性原癌基因网络导致 PTEN 丢失和肿瘤发生。
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10
A whole-genome RNAi screen identifies an 8q22 gene cluster that inhibits death receptor-mediated apoptosis.全基因组 RNAi 筛选鉴定出一个抑制死亡受体介导的细胞凋亡的 8q22 基因簇。
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