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Long noncoding RNA cytoskeleton regulator RNA promotes cell invasion and metastasis by titrating miR-613 to regulate ANXA2 in nasopharyngeal carcinoma.
Cancer Medicine ( IF 4 ) Pub Date : 2019-12-20 , DOI: 10.1002/cam4.2778
Wei Chen 1 , Mingyu Du 1 , Xinyu Hu 1 , Hongxia Ma 2 , Erbao Zhang 2 , Tingting Wang 1 , Li Yin 1 , Xia He 1 , Zhibin Hu 2
Affiliation  

BACKGROUND Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors. Long noncoding RNAs play critical roles in tumorigenesis. METHODS Real-time quantitative PCR arrays were used to evaluate the expression levels of cytoskeleton regulator RNA (CYTOR) in NPC tissues and cells. Cell counting kit-8 and colony formation analyses were used to test the NPC cell viability, while wound healing and transwell assays were employed to detect cell invasion and migration ability. Luciferase reporter assay and Western blot analyses were employed to explore the relationships among CYTOR, miR-613, and ANXA2. RESULTS We found that CYTOR expression was elevated both in NPC tissues and cells. Functional assays revealed that CYTOR promoted the invasion and migration of NPC cells. The established spontaneous lymph node metastasis model also confirmed that CYTOR promoted NPC cell metastasis in vivo. Mechanically, we found that the subcellular localization of CYTOR mostly occurred in the cell cytoplasm. Luciferase reporter and RIP assays confirmed that CYTOR functioned as the molecular sponge of miR-613. Subsequent experiments confirmed that ANXA2 was directly targeted by miR-613. Gain- and loss-of-function studies further confirmed that CYTOR induced the upregulation of ANXA2 by competitively binding to miR-613, thus leading to NPC metastasis. CONCLUSION Our results highlight the importance of CYTOR in NPC development and provide new insights into potential therapeutic targets for NPC.

中文翻译:

长的非编码RNA细胞骨架调节剂RNA通过滴定miR-613调节鼻咽癌中的ANXA2来促进细胞侵袭和转移。

背景技术鼻咽癌(NPC)是最常见的头颈部恶性肿瘤之一。长的非编码RNA在肿瘤发生中起关键作用。方法采用实时定量PCR芯片评估NPC组织和细胞中细胞骨架调节子RNA(CYTOR)的表达水平。细胞计数试剂盒8和集落形成分析用于测试NPC细胞的活力,而伤口愈合和transwell分析用于检测细胞的侵袭和迁移能力。采用荧光素酶报告基因分析和Western印迹分析来探讨CYTOR,miR-613和ANXA2之间的关系。结果我们发现CYTOR表达在NPC组织和细胞中均升高。功能测定表明CYTOR促进了NPC细胞的侵袭和迁移。建立的自发性淋巴结转移模型也证实了CYTOR在体内促进了NPC细胞转移。在机械上,我们发现CYTOR的亚细胞定位主要发生在细胞质中。萤光素酶报告基因和RIP分析证实CYTOR充当miR-613的分子海绵。随后的实验证实了miR-613直接靶向ANXA2。功能获得和功能丧失研究进一步证实,CYTOR通过与miR-613竞争性结合诱导ANXA2的上调,从而导致NPC转移。结论我们的结果突出了CYTOR在鼻咽癌发展中的重要性,并为鼻咽癌的潜在治疗靶标提供了新的见解。我们发现CYTOR的亚细胞定位主要发生在细胞质中。萤光素酶报告基因和RIP分析证实CYTOR充当miR-613的分子海绵。随后的实验证实了miR-613直接靶向ANXA2。功能获得和功能丧失研究进一步证实,CYTOR通过与miR-613竞争性结合诱导ANXA2的上调,从而导致NPC转移。结论我们的结果突出了CYTOR在鼻咽癌发展中的重要性,并为鼻咽癌的潜在治疗靶标提供了新的见解。我们发现CYTOR的亚细胞定位主要发生在细胞质中。萤光素酶报告基因和RIP分析证实CYTOR充当miR-613的分子海绵。随后的实验证实了miR-613直接靶向ANXA2。功能获得和功能丧失研究进一步证实,CYTOR通过与miR-613竞争性结合诱导ANXA2的上调,从而导致NPC转移。结论我们的结果突出了CYTOR在鼻咽癌发展中的重要性,并为鼻咽癌的潜在治疗靶标提供了新的见解。功能获得和功能丧失研究进一步证实,CYTOR通过与miR-613竞争性结合诱导ANXA2的上调,从而导致NPC转移。结论我们的结果突出了CYTOR在鼻咽癌发展中的重要性,并为鼻咽癌的潜在治疗靶标提供了新的见解。功能获得和功能丧失研究进一步证实,CYTOR通过与miR-613竞争性结合诱导ANXA2的上调,从而导致NPC转移。结论我们的结果突出了CYTOR在鼻咽癌发展中的重要性,并为鼻咽癌的潜在治疗靶标提供了新的见解。
更新日期:2019-12-20
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