Hypoxia-induced long noncoding RNA NR2F1-AS1 maintains pancreatic cancer proliferation, migration, and invasion by activating the NR2F1/AKT/mTOR axis.
Hypoxia-induced long noncoding RNA NR2F1-AS1 maintains pancreatic cancer proliferation, migration, and invasion by activating the NR2F1/AKT/mTOR axis.
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缺氧诱导的长非编码RNA NR2F1-AS1通过激活NR2F1/AKT/mTOR轴维持胰腺癌的增殖、迁移和侵袭
DOI：
10.1038/s41419-022-04669-0
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发表时间：
2022-03-14
影响因子：
9
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Liu Y;Chen S;Cai K;Zheng D;Zhu C;Li L;Wang F;He Z;Yu C;Sun C
越来越多的证据表明，长链非编码rna （lncRNAs）在包括胰腺癌（PC）在内的各种类型的人类癌症中发挥着重要作用。然而，核受体亚家族2组F成员1反义RNA 1 （NR2F1-AS1）在PC细胞恶性进展中的作用及其调控机制仍有待研究。本研究通过体外和体内实验研究NR2F1- as1和NR2F1在PC中的生物学效应。通过生物信息学预测分析和验证性实验监测NR2F1-AS1的作用机制。我们的研究结果表明NR2F1-AS1在PC中过表达，并与生存不良呈正相关。在体外和体内实验中，NR2F1-AS1的缺失抑制了PC细胞的增殖、迁移、侵袭，抑制了异种移植物肿瘤的生长和转移。机制实验表明，NR2F1- as1正调控邻近的NR2F1基因，激活AKT/mTOR信号通路，导致缺氧诱导因子-1α (HIF-1α)上调。进一步的研究表明，缺氧条件下NR2F1-AS1的表达受HIF-1α的转录调控。这些发现表明，缺氧诱导的NR2F1- as1表达直接增加NR2F1水平，通过激活AKT/mTOR信号通路促进PC细胞增殖、迁移和侵袭。总之，这些发现表明NR2F1-AS1可能是PC的前瞻性治疗靶点。
Accumulating evidence has demonstrated the essential role of long noncoding RNAs (lncRNAs) in various types of human cancer, including pancreatic cancer (PC). However, the functions and regulatory mechanisms of nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) that are responsible for its role in the malignant progression of PC cells remains to be investigated. In this study, the biological effects of NR2F1-AS1 and NR2F1 in PC were investigated by in vitro and in vivo experiments. The mechanisms of NR2F1-AS1 were monitored by bioinformatic predictive analysis and confirmatory experiments. Our results indicated that NR2F1-AS1 was overexpressed and positively correlated with poor survival in PC. Depletion of NR2F1-AS1 restrained PC cell proliferation, migration, invasion, and suppressed xenograft tumor growth and metastasis in vitro and in vivo. Mechanistic experiments suggested that NR2F1-AS1 positively regulated the neighboring NR2F1 gene, which subsequently activated AKT/mTOR signaling, resulting in the upregulation of hypoxia-inducible factor-1α (HIF-1α). Further investigations elucidated that NR2F1-AS1 expression was transcriptionally regulated by HIF-1α under hypoxia. These findings demonstrated that hypoxia-induced NR2F1-AS1 expression directly increased NR2F1 levels to promote PC cell proliferation, migration, and invasion by activating AKT/mTOR signaling. Together, these findings suggest that NR2F1-AS1 could be a prospective therapeutic target for PC.
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DOI：
10.1038/nrc.2017.99
发表时间：
2018-01
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Anastasiadou E;Jacob LS;Slack FJ
通讯作者：
Slack FJ
影响因子：
3.3
作者：
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影响因子：
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作者：
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Luo L
DOI：
10.1038/s41580-020-00315-9
发表时间：
2021-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Statello L;Guo CJ;Chen LL;Huarte M
通讯作者：
Huarte M
影响因子：
5.2
作者：
Li, Shenglong;Zheng, Ke;Zhang, Xiaojing
通讯作者：
Zhang, Xiaojing