长链非编码RNA CADM2-AS1通过与miR-5047结合并激活NOTCH4翻译来促进胃癌转移。
The lncRNA CADM2-AS1 promotes gastric cancer metastasis by binding with miR-5047 and activating NOTCH4 translation.
作者信息
Zhang Yu-Tong, Zhao Li-Juan, Zhou Teng, Zhao Jin-Yuan, Geng Yin-Ping, Zhang Qiu-Rong, Sun Pei-Chun, Chen Wen-Chao
机构信息
Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, Henan University People's Hospital, Zhengzhou University People's Hospital, Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China.
State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
出版信息
Front Pharmacol. 2024 Sep 6;15:1439497. doi: 10.3389/fphar.2024.1439497. eCollection 2024.
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 and . 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 and . 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.
背景
多器官转移一直是胃癌（GC）患者死亡的主要原因。转移性GC患者的预后仍然很差。长期以来，长链非编码RNA（lncRNAs）一直被报道与癌症转移密切相关。
方法
本文通过lncRNA测序在临床淋巴结转移GC组织中鉴定出异常表达的lncRNA CADM2-AS1。此外，通过Transwell、伤口愈合、蛋白质免疫印迹或其他检测方法检测lncRNA CADM2-AS1在癌症转移中的作用。通过RNA荧光原位杂交、双荧光素酶报告基因检测和逆转录定量聚合酶链反应进行进一步的机制研究。最后，通过逆转录定量聚合酶链反应检测患者组织中lncRNA CADM2-AS1、miR-5047和NOTCH4之间的关系。
结果
本文通过lncRNA测序在临床淋巴结转移GC组织中鉴定出异常表达的lncRNA CADM2-AS1。此外，检测了lncRNA CADM2-AS1在癌症转移中的作用。结果表明，lncRNA CADM2-AS1的过表达促进了GC转移，而敲低则抑制了GC转移。进一步的机制研究证明，lncRNA CADM2-AS1可以吸附并沉默miR-5047，其靶向的mRNA是NOTCH4。lncRNA CADM2-AS1的表达升高通过上调NOTCH4 mRNA水平促进GC转移。此外，在转移性GC患者组织中进一步检测并验证了lncRNA CADM2-AS1、miR-5047和NOTCH4之间的关系。
结论
lncRNA CADM2-AS1通过靶向miR-5047/NOTCH4信号轴促进GC转移，这可能是GC转移的一个潜在靶点。
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