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抑制端锚聚合酶1通过调节人端粒酶逆转录酶和端粒重复序列结合因子1来抑制胃腺癌的进展。

Knockdown of tankyrase 1 inhibits the progression of gastric adenocarcinoma via regulating human telomerase reverse transcriptase and telomeric repeat binding factor 1.

作者信息

Liu Wei, Zhu Ji-Jun, Liu Yun-Yun, Tang Na-Na, Wang Yan, Jiang Bo, Wang Li-Li, Wang Yu-Xin, Xie Min-Peng, Wang Xiao-Yan

机构信息

Department of Gastroenterology, Suqian First Hospital, Suqian, China.

出版信息

J Gastrointest Oncol. 2022 Apr;13(2):559-568. doi: 10.21037/jgo-22-82.


DOI:10.21037/jgo-22-82
PMID:35557584
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9086053/
Abstract

BACKGROUND: Gastric cancer is one of the most lethal cancers. Aberrant expression levels of genes are frequently associated with cell immortalization and the occurrence of tumors. In this study, we aimed to investigate the role of tankyrase 1 () in gastric adenocarcinoma and clarify the underlying mechanism. METHODS: The messenger RNA (mRNA) levels of , human telomerase reverse transcriptase (), and telomeric repeat binding factor 1 () in clinical specimens and SGC-7901 cells were measured via real-time quantitative polymerase chain reaction (RT-qPCR). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemistry (IHC) assays were utilized to observe the cell apoptosis as well as Ki67 and expression in tumor-bearing models. The effects of antisense oligonucleotides (TANK1 ASODN) on viability and apoptosis of SGC 7901 cells were evaluated by cell counting kit-8 and flow cytometry analysis. RESULTS: We found that and were both increased in gastric adenocarcinoma, while was decreased. Tumor-bearing models demonstrated that TANK1 ASODN appeared to be effective in inhibiting tumor growth and decreasing the expression of . Additionally, TANK1 ASODN inhibited the viability and promoted apoptosis of SGC-7901 cells. Moreover, the mRNA levels of and were modulated by TANK1 ASODN. CONCLUSIONS: This study revealed that TANK1 ASODN inhibits the proliferation and induced the apoptosis of gastric adenocarcinoma cells via manipulating the expression levels of and .

摘要

背景:胃癌是最致命的癌症之一。基因表达水平异常常与细胞永生化和肿瘤发生相关。在本研究中,我们旨在探讨端锚聚合酶1(TNKS1)在胃腺癌中的作用并阐明其潜在机制。 方法:通过实时定量聚合酶链反应(RT-qPCR)检测临床标本和SGC-7901细胞中TNKS1、人端粒酶逆转录酶(hTERT)和端粒重复结合因子1(TRF1)的信使核糖核酸(mRNA)水平。利用末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)和免疫组织化学(IHC)分析观察荷瘤模型中的细胞凋亡以及Ki67和hTERT表达。通过细胞计数试剂盒-8和流式细胞术分析评估TNKS1反义寡核苷酸(TANK1 ASODN)对SGC 7901细胞活力和凋亡的影响。 结果:我们发现胃腺癌中TNKS1和hTERT均升高,而TRF1降低。荷瘤模型表明TANK1 ASODN似乎能有效抑制肿瘤生长并降低hTERT表达。此外,TANK1 ASODN抑制SGC-7901细胞的活力并促进其凋亡。而且,TANK1 ASODN调节了hTERT和TRF1的mRNA水平。 结论:本研究表明,TANK1 ASODN通过调控hTERT和TRF1的表达水平抑制胃腺癌细胞的增殖并诱导其凋亡。

相似文献

[1]
Knockdown of tankyrase 1 inhibits the progression of gastric adenocarcinoma via regulating human telomerase reverse transcriptase and telomeric repeat binding factor 1.

J Gastrointest Oncol. 2022-4

[2]
[Preliminary research on the effect of antisense oligodeoxynucleotides of tankyrase 1 on tumor growth following intratumoral injection in mice].

Zhonghua Jie He He Hu Xi Za Zhi. 2004-9

[3]
Expression of telomeric repeat binding factor 1 and 2 and TRF1-interacting nuclear protein 2 in human gastric carcinomas.

Int J Oncol. 2001-9

[4]
Expression of MRE11 complex (MRE11, RAD50, NBS1) and hRap1 and its relation with telomere regulation, telomerase activity in human gastric carcinomas.

Pathobiology. 2001

[5]
Altered mRNA expression of telomere-associated genes in monoclonal gammopathy of undetermined significance and multiple myeloma.

Mol Med. 2010-7-14

[6]
The expression of telomeric proteins and their probable regulation of telomerase during the differentiation of all-trans-retinoic acid-responsive and -resistant acute promyelocytic leukemia cells.

Int J Hematol. 2005-10

[7]
Tankyrase1 antisense oligodeoxynucleotides suppress the proliferation, migration and invasion through Hippo/YAP pathway in human osteosarcoma cells.

Pathol Res Pract. 2019-3-5

[8]
Coordinate regulation between expression levels of telomere-binding proteins and telomere length in breast carcinomas.

Cancer Med. 2012-7-24

[9]
TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression.

J Biol Chem. 2001-9-21

[10]
Tankyrase promotes telomere elongation in human cells.

Curr Biol. 2000-10-19

本文引用的文献

[1]
Epidemiological Trends and Future Perspectives of Gastric Cancer in Eastern Asia.

Digestion. 2022

[2]
Lifestyles, genetics, and future perspectives on gastric cancer in east Asian populations.

J Hum Genet. 2021-9

[3]
Loss of p16 and high Ki67 labeling index is associated with poor outcome in esophageal carcinoma.

Oncotarget. 2020-3-24

[4]
THE STUDY OF THE EXPRESSION OF CDH1, KI67, P53 AND HER2 IN DIFFUSE GASTRIC CARCINOMA.

Georgian Med News. 2020-2

[5]
Tankyrases/β-catenin Signaling Pathway as an Anti-proliferation and Anti-metastatic Target in Hepatocarcinoma Cell Lines.

J Cancer. 2020-1-1

[6]
Tankyrase disrupts metabolic homeostasis and promotes tumorigenesis by inhibiting LKB1-AMPK signalling.

Nat Commun. 2019-9-25

[7]
Tankyrase1 antisense oligodeoxynucleotides suppress the proliferation, migration and invasion through Hippo/YAP pathway in human osteosarcoma cells.

Pathol Res Pract. 2019-3-5

[8]
Tankyrase Promotes Aerobic Glycolysis and Proliferation of Ovarian Cancer through Activation of Wnt/-Catenin Signaling.

Biomed Res Int. 2019-2-20

[9]
Inhibition of tankyrase by a novel small molecule significantly attenuates prostate cancer cell proliferation.

Cancer Lett. 2018-11-22

[10]
IWR-1, a tankyrase inhibitor, attenuates Wnt/β-catenin signaling in cancer stem-like cells and inhibits in vivo the growth of a subcutaneous human osteosarcoma xenograft.

Cancer Lett. 2017-11-8

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