A novel oncogenic seRNA promotes nasopharyngeal carcinoma metastasis.
A novel oncogenic seRNA promotes nasopharyngeal carcinoma metastasis.
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一种新型致癌seRNA促进鼻咽癌转移。
DOI：
10.1038/s41419-022-04846-1
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发表时间：
2022-04-23
影响因子：
9
通讯作者：
Tang, Faqing
中科院分区：
文献类型：
--
作者：
Tan, Yuan;Jiang, Chonghua;Jia, Qunying;Wang, Jing;Huang, Ge;Tang, Faqing
鼻咽癌（Nasopharyngeal carcinoma，NPC）是我国南方常见的恶性肿瘤，具有高度侵袭性和转移性，死亡率高，但其发病机制尚不清楚。在本研究中，我们利用ChIP-Seq鉴定了转移特异性超级增强子（SE），发现LOC 100506178的SE仅存在于转移性NPC细胞中，并且有力地加重了NPC转移。该转移性SE转录成lncRNA L0 C100506178，并且通过GRO-Seq验证其为seRNA。此外，发现SE衍生的seRNA LOC 100506178在转移性NPC细胞和NPC淋巴结转移组织中高度表达。SeRNA LOC 100506178的敲低在体外和体内均能抑制NPC细胞的侵袭和转移，表明seRNA LOC 100506178可加速NPC恶性表型的获得。机制研究表明，seRNA LOC 100506178特异性地与转录因子hnRNPK相互作用并调节hnRNPK的表达。此外，hnRNPK与MICAL 2的启动子区域组合增加Mical 2转录。SeRNA LOC 100506178或hnRNPK的敲低显著抑制MICAL 2、波形蛋白和Snail表达，并上调E-钙粘蛋白表达。seRNA LOC 100506178或hnRNPK的过表达显著增加MICAL 2、波形蛋白和Snail的表达，并降低E-钙粘蛋白的表达。因此，seRNA LOC 100506178可能通过上调hnRNPK促进MICAL 2表达，进而促进EMT过程，加速NPC细胞的侵袭和转移。seRNA L0 C100506178有可能作为NPC患者的新的预后生物标志物和治疗靶点。
Nasopharyngeal carcinoma (NPC) is a common malignant cancer in southern China that has highly invasive and metastatic features and causes high mortality, but the underlying mechanisms of this malignancy remain unclear. In this study, we utilized ChIP-Seq to identify metastasis-specific super enhancers (SEs) and found that the SE of LOC100506178 existed only in metastatic NPC cells and powerfully aggravated NPC metastasis. This metastatic SE transcribed into lncRNA LOC100506178, and it was verified as a seRNA through GRO-Seq. Furthermore, SE-derived seRNA LOC100506178 was found to be highly expressed in metastatic NPC cells and NPC lymph node metastatic tissues. Knockdown of seRNA LOC100506178 arrested the invasion and metastasis of NPC cells in vitro and in vivo, demonstrating that seRNA LOC100506178 accelerates the acquisition of NPC malignant phenotype. Mechanistic studies revealed that seRNA LOC100506178 specifically interacted with the transcription factor hnRNPK and modulated the expression of hnRNPK. Further, hnRNPK in combination with the promoter region of MICAL2 increased Mical2 transcription. Knockdown of seRNA LOC100506178 or hnRNPK markedly repressed MICAL2, Vimentin and Snail expression and upregulated E-cadherin expression. Overexpression of seRNA LOC100506178 or hnRNPK markedly increased MICAL2, Vimentin and Snail expression and decreased E-cadherin expression. Therefore, seRNA LOC100506178 may promote MICAL2 expression by upregulating hnRNPK, subsequently enhancing EMT process and accelerating the invasion and metastasis of NPC cells. seRNA LOC100506178 has the potential to serve as a novel prognostic biomarker and therapeutic target in NPC patients.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
6
作者：
Lim, Ratana;Nguyen-Ngo, Caitlyn;Lappas, Martha
通讯作者：
Lappas, Martha
DOI：
10.1093/bioinformatics/btr490
发表时间：
2011-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Howe EA;Sinha R;Schlauch D;Quackenbush J
通讯作者：
Quackenbush J
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
7.3
作者：
Fung, Tsun Ming;Ng, Kai Yu;Ma, Stephanie
通讯作者：
Ma, Stephanie