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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1439497
This article is part of the Research Topic Novel Anti-Cancer Agents Targeting Tumour Metastasis and Stemness View all 8 articles
The lncRNA CADM2-AS1 promotes gastric cancer metastasis by binding with miR-5047 and activating NOTCH4 translation
Provisionally accepted- 1 Zhengzhou University, Zhengzhou, Henan Province, China
- 2 Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
- 3 Henan Provincial People's Hospital, Zhengzhou, Henan Province, China
Abstract Background: Multi-organ metastasis has been the main cause of death in patients with Gastric cancer (GC). The prognosis for patients with metastasized GC is still very poor. Long noncoding RNAs (lncRNAs) always been reported to be closely related to cancer metastasis. Methods: In this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected by Transwell, Wound healing, Western Blot or other assays in vitro and in vivo. Further mechanism study was performed by RNA FISH, Dual-luciferase reporter assay and RT-qPCR. Finally, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 in patient tissues was detected by RT-qPCR. Results: In this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected in vitro and in vivo. The results shown that overexpression of the lncRNA CADM2-AS1 promoted GC metastasis, while knockdown inhibited it. Further mechanism study proved that lncRNA CADM2-AS1 could sponge and silence miR-5047, which targeting mRNA was NOTCH4. Elevated expression of lncRNA CADM2-AS1 facilitate GC metastasis by up-regulating NOTCH4 mRNA level consequently. What's more, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 was further detected and verified in metastatic GC patient tissues. Conclusions: LncRNA CADM2-AS1 promoted metastasis in GC by targeting the miR-5047/ NOTCH4 signaling axis, which may be a potential target for GC metastasis.
Keywords: lncRNA CADM2-AS1, gastric cancer, metastasis, NOTCH4, miR-5047
Received: 28 May 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Zhang, Zhao, Zhou, Zhao, Geng, Zhang, Liu, Sun and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yu-Tong Zhang, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
Teng Zhou, Henan Provincial People's Hospital, Zhengzhou, 450000, Henan Province, China
Jin-Yuan Zhao, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
Yin-Ping Geng, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
Qiu-Rong Zhang, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
Hong-Min Liu, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
Pei-Chun Sun, Henan Provincial People's Hospital, Zhengzhou, 450000, Henan Province, China
Wen-Chao Chen, Henan Provincial People's Hospital, Zhengzhou, 450000, Henan Province, China
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