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长链非编码 RNA LINC00649 通过招募 TAF15 并增强 MAPK6 的表达来激活 MAPK 信号通路,从而促进肺鳞癌的发展。

LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway.

机构信息

Department of Thoracic Surgery, Shandong Provincial Chest Hospital, Jinan, 250100, Shandong, China.

Department of Cardio-Thoracic Surgery, Shandong Provincial Chest Hospital, Jinan, 250100, Shandong, China.

出版信息

Cancer Gene Ther. 2022 Aug;29(8-9):1285-1295. doi: 10.1038/s41417-021-00410-9. Epub 2022 Feb 28.

DOI:10.1038/s41417-021-00410-9
PMID:35228660
Abstract

Lung squamous cell carcinoma (LUSC) represents one of the commonest types of lung cancer featured with high morbidity and poor prognosis. Many types of research have documented that long noncoding RNAs (lncRNAs) exert crucial functions in the development of cancers, and LUSC is included. In our study, we aimed at unveiling the mechanism underlying long intergenic nonprotein coding RNA 0649 (LINC00649) in LUSC cells. As a result, LINC00649 was discovered to be with high expression in LUSC cells. Moreover, it was confirmed through functional assays that the knockdown of LINC00649 hindered the occurrence and progression of LUSC. Results of mechanism assays validated that E2F transcription factor 7 (E2F7) was a transcription activator of LINC00649 and induced its up-regulation in LUSC cells. Furthermore, LINC00649 recruited TAF15, which is TATA-box binding protein associated factor 15 to stabilize mitogen-activated protein kinase 6 (MAPK6) expression and activate the transcription of MAPK6, thereby enhancing MAPK6 expression to activate the MAPK signaling pathway. Eventually, results of rescue assays suggested that overexpression of MAPK6 offset the influence of LINC00649 silencing on LUSC progression. In summary, our research determined the E2F7/LINC00649/TAF15/MAPK6/MAPK signaling pathway in regulating LUSC development, which made LINC00649 a potential biomarker for LUSC treatment.

摘要

肺鳞状细胞癌(LUSC)是最常见的肺癌类型之一,其发病率高,预后差。许多类型的研究已经证明,长非编码 RNA(lncRNA)在癌症的发展中发挥着关键作用,LUSC 也包括在内。在我们的研究中,我们旨在揭示长非编码基因 0649(LINC00649)在 LUSC 细胞中的作用机制。结果发现,LINC00649 在 LUSC 细胞中表达水平较高。此外,通过功能测定证实,敲低 LINC00649 抑制了 LUSC 的发生和进展。机制测定结果验证了 E2F 转录因子 7(E2F7)是 LINC00649 的转录激活因子,诱导其在 LUSC 细胞中上调。此外,LINC00649 募集 TAF15,即 TATA 盒结合蛋白相关因子 15,以稳定丝裂原激活蛋白激酶 6(MAPK6)的表达并激活 MAPK6 的转录,从而增强 MAPK6 的表达以激活 MAPK 信号通路。最终,挽救测定结果表明,MAPK6 的过表达抵消了 LINC00649 沉默对 LUSC 进展的影响。总之,我们的研究确定了 E2F7/LINC00649/TAF15/MAPK6/MAPK 信号通路在调节 LUSC 发展中的作用,这使得 LINC00649 成为 LUSC 治疗的潜在标志物。

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