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靶向YAP1/LINC00152/FSCN1信号轴可预防结直肠癌进展。

Targeting YAP1/LINC00152/FSCN1 Signaling Axis Prevents the Progression of Colorectal Cancer.

作者信息

Ou Chunlin, Sun Zhenqiang, He Xiaoyun, Li Xiaoling, Fan Songqing, Zheng Xiang, Peng Qiu, Li Guiyuan, Li Xiayu, Ma Jian

机构信息

Xiangya Hospital Department of Pathology Cancer Research Institute Central South University Changsha Hunan 410008 China.

Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education Central South University Changsha 410078 China.

出版信息

Adv Sci (Weinh). 2019 Dec 5;7(3):1901380. doi: 10.1002/advs.201901380. eCollection 2020 Feb.

DOI:10.1002/advs.201901380
PMID:32042551
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7001651/
Abstract

As a transcription coactivator, Yes-associated protein 1 (YAP1)'s role in tumorigenesis is well established. However, the mechanism of YAP1-regulating long noncoding RNAs (lncRNA) in tumors is still largely unknown. Here, a YAP1 target gene, long intergenic noncoding RNA 00152 (LINC00152), which is highly expressed in colorectal cancer (CRC), is identified. The oncogenic functions of LINC00152 in CRC are demonstrated by a panel of in vitro and in vivo experiments. Further studies reveal the potential downstream mechanisms of LINC00152, which can act as a competing endogenous RNA sponging with miR-632 and miR-185-3p to regulate Fascin actin-bundling protein 1 (FSCN1) expression and thus promote the malignant proliferation and metastasis in CRC cells. Targeting the YAP1/LINC00152/FSCN1 axis inhibits the progression of CRC. This finding provides a new regulatory model of the "YAP1-lncRNA" in CRC, which gives rise to a new perspective, "YAP1/LINC00152/miR-632-miR-185-3p/FSCN1," to explore the cancer-promoting mechanism of YAP1 involved in CRC.

摘要

作为一种转录共激活因子，Yes相关蛋白1（YAP1）在肿瘤发生中的作用已得到充分证实。然而，YAP1在肿瘤中调控长链非编码RNA（lncRNA）的机制仍在很大程度上未知。在此，鉴定出一个YAP1靶基因，即长链基因间非编码RNA 00152（LINC00152），其在结直肠癌（CRC）中高表达。一系列体外和体内实验证实了LINC00152在CRC中的致癌功能。进一步研究揭示了LINC00152潜在的下游机制，它可作为一种竞争性内源性RNA，与miR-632和miR-185-3p结合，从而调控丝状肌动蛋白成束蛋白1（FSCN1）的表达，进而促进CRC细胞的恶性增殖和转移。靶向YAP1/LINC00152/FSCN1轴可抑制CRC的进展。这一发现为CRC中“YAP1-lncRNA”提供了一种新的调控模式，为探索YAP1参与CRC的促癌机制提供了一个新的视角，即“YAP1/LINC00152/miR-632-miR-185-3p/FSCN1”。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/afe2fbe86cc5/ADVS-7-1901380-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/362d44bff918/ADVS-7-1901380-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/98d539443261/ADVS-7-1901380-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/6a7f0f9cc1e6/ADVS-7-1901380-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/658ac6f45bf9/ADVS-7-1901380-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/eaec6e190a35/ADVS-7-1901380-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/fe5c482539cc/ADVS-7-1901380-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/afe2fbe86cc5/ADVS-7-1901380-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/362d44bff918/ADVS-7-1901380-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/98d539443261/ADVS-7-1901380-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/6a7f0f9cc1e6/ADVS-7-1901380-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/658ac6f45bf9/ADVS-7-1901380-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/eaec6e190a35/ADVS-7-1901380-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/fe5c482539cc/ADVS-7-1901380-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d18/7001651/afe2fbe86cc5/ADVS-7-1901380-g007.jpg

相似文献

[1]
Targeting YAP1/LINC00152/FSCN1 Signaling Axis Prevents the Progression of Colorectal Cancer.

Adv Sci (Weinh). 2019-12-5

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[10]
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本文引用的文献

[1]
YAP1-induced MALAT1 promotes epithelial-mesenchymal transition and angiogenesis by sponging miR-126-5p in colorectal cancer.

Oncogene. 2018-12-10

[2]
Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis.

J Exp Clin Cancer Res. 2018-11-27

[3]
FOXA1 reprograms the TGF-β-stimulated transcriptional program from a metastasis promoter to a tumor suppressor in nasopharyngeal carcinoma.

Cancer Lett. 2018-10-28

[4]
Blocking LINC00152 suppresses glioblastoma malignancy by impairing mesenchymal phenotype through the miR-612/AKT2/NF-κB pathway.

J Neurooncol. 2018-7-24

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A Positive Feed-Forward Loop between LncRNA-CYTOR and Wnt/β-Catenin Signaling Promotes Metastasis of Colon Cancer.

Mol Ther. 2018-3-6

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Suppression Colitis and Colitis-Associated Colon Cancer by Anti-S100a9 Antibody in Mice.

Front Immunol. 2017-12-13

[7]
Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression.

Theranostics. 2017-10-17

[8]
Functional Role of a Novel Long Noncoding RNA in Esophageal Squamous Cell Carcinoma Progression and Metastasis.

Clin Cancer Res. 2017-11-3

[9]
LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism.

EMBO J. 2017-11-15

[10]
Myc target gene, long intergenic noncoding RNA, Linc00176 in hepatocellular carcinoma regulates cell cycle and cell survival by titrating tumor suppressor microRNAs.

Oncogene. 2017-9-4

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