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长链非编码RNA MDC1-AS通过MDC1依赖性机制抑制人胃癌细胞的增殖和转移。

Long non-coding RNA MDC1-AS inhibits human gastric cancer cell proliferation and metastasis through an MDC1-dependent mechanism.

作者信息

Qin Ying, Zhuang Shutong, Wen Jianfeng, Zheng Kai

机构信息

Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518029, P.R. China.

出版信息

Exp Ther Med. 2018 Jan;15(1):191-197. doi: 10.3892/etm.2017.5370. Epub 2017 Oct 24.

DOI:10.3892/etm.2017.5370
PMID:29375682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5763657/
Abstract

Gastric cancer is the third leading cause of cancer-associated mortality worldwide and is one of the most common malignancies in China. However, the molecular mechanisms underlying the tumorigenesis of gastric cancer remain largely unclear. Long non-coding (Lnc)RNAs have been demonstrated to serve significant roles in the tumorigenesis of various types of cancer. The present study aimed to explore the role of the LncRNA mediator of DNA damage checkpoint protein 1-antisense RNA (MDC1-AS), the antisense transcript of MDC1, in human gastric cancer. The results revealed that the expression of MDC1-AS in human gastric cancer was significantly suppressed and . In addition, overexpression of MDC1-AS in the poorly differentiated gastric cancer cell line MKN28 significantly inhibited cell proliferation and metastasis, while the knockdown of MDC1-AS in well-differentiated MKN45 gastric cancer cells significantly increased proliferation and metastasis. The knockdown of MDC1 relieved the inhibitory effect of MDC1-AS on MKN28 cell proliferation and metastasis, while the overexpression of MDC1 attenuated the stimulatory effect of MDC1-AS knockdown in MKN45 cells. Thus, the present study demonstrated that MDC1-AS had an inhibitory on gastric tumorigenesis through an MDC1-dependent mechanism. This indicates that MDC1-AS is a potential novel therapeutic target for the diagnosis and treatment of human gastric cancer in the clinic.

摘要

胃癌是全球癌症相关死亡的第三大主要原因，也是中国最常见的恶性肿瘤之一。然而，胃癌发生的分子机制仍 largely不清楚。长链非编码（Lnc）RNA已被证明在各种类型癌症的发生中起重要作用。本研究旨在探讨DNA损伤检查点蛋白1反义RNA（MDC1-AS），即MDC1的反义转录本，在人类胃癌中的作用。结果显示，MDC1-AS在人类胃癌中的表达被显著抑制。此外，在低分化胃癌细胞系MKN28中过表达MDC1-AS显著抑制细胞增殖和转移，而在高分化MKN45胃癌细胞中敲低MDC1-AS则显著增加增殖和转移。敲低MDC1可缓解MDC1-AS对MKN28细胞增殖和转移的抑制作用，而MDC1的过表达则减弱了MDC1-AS敲低对MKN45细胞的刺激作用。因此，本研究表明MDC1-AS通过依赖MDC1的机制对胃癌发生具有抑制作用。这表明MDC1-AS是临床上诊断和治疗人类胃癌的潜在新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/b962325743e5/etm-15-01-0191-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/0550f847e9c7/etm-15-01-0191-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/efba4850d4a1/etm-15-01-0191-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/4f00b23a7e83/etm-15-01-0191-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/fd692d68604c/etm-15-01-0191-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/b962325743e5/etm-15-01-0191-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/0550f847e9c7/etm-15-01-0191-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/efba4850d4a1/etm-15-01-0191-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/4f00b23a7e83/etm-15-01-0191-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/fd692d68604c/etm-15-01-0191-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b9/5763657/b962325743e5/etm-15-01-0191-g04.jpg

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