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长链非编码RNA HAS2-AS1通过靶向LSD1/EphB3通路加速非小细胞肺癌化疗耐药

Long noncoding RNA HAS2-AS1 accelerates non-small cell lung cancer chemotherapy resistance by targeting LSD1/EphB3 pathway.

作者信息

Sun Peng, Sun Limin, Cui Jia, Liu Lili, He Qing

机构信息

Department of Oncology, The Second Hospital of Dalian Medical University Dalian, China.

出版信息

Am J Transl Res. 2020 Mar 15;12(3):950-958. eCollection 2020.

PMID:32269726
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7137060/
Abstract

The essential roles of long noncoding RNA (lncRNA) have been identified by emerging literature in the non-small cell lung cancer (NSCLC). However, the role of lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) in the NSCLC tumorigenesis is not clear. Here, we investigate the role and mechanism of HAS2-AS1 in the NSCLC tumorigenesis. In the NSCLC tissue and cells, HAS2-AS1 was found to be up-regulated, which, in turn, indicated the poor prognosis of NSCLC patients. Functional experiments illustrated that HAS2-AS1 promoted the proliferation, invasion and gefitinib chemotherapy resistance of NSCLC cells. In , HAS2-AS1 knockdown suppressed the tumor growth. Mechanically, HAS2-AS1 recruited the lysine-specific demethylase 1 (LSD1) to the EphB3 promoter region to inhibit its transcription. In conclusion, this finding elucidates the essential roles of HAS2-AS1 in the NSCLC tumorigenesis, providing a possible treatment strategy for the NSCLC.

摘要

长链非编码RNA(lncRNA)的重要作用已被非小细胞肺癌(NSCLC)领域不断涌现的文献所证实。然而,lncRNA透明质酸合酶2反义1(HAS2-AS1)在NSCLC肿瘤发生中的作用尚不清楚。在此,我们研究了HAS2-AS1在NSCLC肿瘤发生中的作用及机制。在NSCLC组织和细胞中,发现HAS2-AS1上调,这反过来表明NSCLC患者预后不良。功能实验表明,HAS2-AS1促进NSCLC细胞的增殖、侵袭和吉非替尼化疗耐药。此外,敲低HAS2-AS1可抑制肿瘤生长。机制上,HAS2-AS1招募赖氨酸特异性去甲基化酶1(LSD1)至EphB3启动子区域以抑制其转录。总之,这一发现阐明了HAS2-AS1在NSCLC肿瘤发生中的重要作用,为NSCLC提供了一种可能的治疗策略。

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LSD1 destabilizes FBXW7 and abrogates FBXW7 functions independent of its demethylase activity.LSD1 使 FBXW7 不稳定,并取消 FBXW7 的功能,而不依赖其去甲基化酶活性。
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CREB1 induced lncRNA HAS2-AS1 promotes epithelial ovarian cancer proliferation and invasion via the miR-466/RUNX2 axis.CREB1 诱导的长链非编码 RNA HAS2-AS1 通过 miR-466/RUNX2 轴促进卵巢上皮性癌细胞的增殖和侵袭。
Biomed Pharmacother. 2019 Jul;115:108891. doi: 10.1016/j.biopha.2019.108891. Epub 2019 May 10.
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LINC00665 Induces Acquired Resistance to Gefitinib through Recruiting EZH2 and Activating PI3K/AKT Pathway in NSCLC.LINC00665通过招募EZH2并激活非小细胞肺癌中的PI3K/AKT通路诱导对吉非替尼的获得性耐药。
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