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Let-7c通过靶向和抑制头颈部鳞状细胞癌的迁移和上皮-间质转化。

Let-7c inhibits migration and epithelial-mesenchymal transition in head and neck squamous cell carcinoma by targeting and .

作者信息

Hou Bo, Ishinaga Hajime, Midorikawa Kaoru, Nakamura Satoshi, Hiraku Yusuke, Oikawa Shinji, Ma Ning, Takeuchi Kazuhiko, Murata Mariko

机构信息

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Mie University, Tsu, Mie 514-8507, Japan.

Department of Environmental and Molecular Medicine, Graduate School of Medicine, Mie University, Tsu, Mie 514-8507, Japan.

出版信息

Oncotarget. 2018 Jan 2;9(10):8927-8940. doi: 10.18632/oncotarget.23826. eCollection 2018 Feb 6.

Abstract

To elucidate the molecular mechanisms underlying the progression of head and neck squamous cell carcinoma (HNSCC), we investigated the function of let-7c as a tumor suppressor. Let-7c expression was significantly down-regulated in HNSCC tumor tissues and cell lines. and studies revealed that let-7c negatively regulated HNSCC proliferation, migration and epithelial-mesenchymal transition (EMT). To explore the underlying mechanisms that affect these molecular events achieved by let-7c, we predicted its target genes. We performed luciferase assay and confirmed that insulin-like growth factor 1 receptor () and high mobility group AT-hook 2 () were the direct targets of let-7c. Knocking down of and inhibited HNSCC progression, including proliferation, migration and EMT in HNSCC cells. Re-expression of these genes overcame let-7c-mediated inhibition. Taken together, our finding suggests that let-7c inhibits HNSCC progression by targeting and and might be a novel target for HNSCC treatment.

摘要

为阐明头颈部鳞状细胞癌(HNSCC)进展的分子机制,我们研究了let-7c作为肿瘤抑制因子的功能。在HNSCC肿瘤组织和细胞系中,let-7c表达显著下调。 研究表明,let-7c负向调节HNSCC的增殖、迁移和上皮-间质转化(EMT)。为探究影响let-7c所引发的这些分子事件的潜在机制,我们预测了其靶基因。我们进行了荧光素酶检测,并证实胰岛素样生长因子1受体(IGF1R)和高迁移率族AT钩蛋白2(HMGA2)是let-7c的直接靶标。敲低IGF1R和HMGA2可抑制HNSCC进展,包括HNSCC细胞的增殖、迁移和EMT。这些基因的重新表达克服了let-7c介导的抑制作用。综上所述,我们的研究结果表明,let-7c通过靶向IGF1R和HMGA2抑制HNSCC进展,可能是HNSCC治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e92b/5823619/0ace10012047/oncotarget-09-8927-g001.jpg

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