Academic Journal

MicroRNA-1224 Inhibits Tumor Metastasis in Intestinal-Type Gastric Cancer by Directly Targeting FAK

التفاصيل البيبلوغرافية
العنوان: MicroRNA-1224 Inhibits Tumor Metastasis in Intestinal-Type Gastric Cancer by Directly Targeting FAK
المؤلفون: Jin Wang, Ti Wen, Zhi Li, Xiaofang Che, Libao Gong, Xianghong Yang, Jingdong Zhang, Huali Tang, Lingzi He, Xiujuan Qu, Yunpeng Liu
المصدر: Frontiers in Oncology, Vol 9 (2019)
بيانات النشر: Frontiers Media S.A., 2019.
سنة النشر: 2019
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: intestinal-type gastric cancer, miR-1224, FAK, metastasis, epithelial-to-mesenchymal transition (EMT), Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Intestinal-type gastric cancer (GC) of the Lauren classification system has specific epidemiological characteristics and carcinogenesis patterns. MicroRNAs (miRNAs) have prognostic significance, and some can be used as prognostic biomarkers in GC. In this study, we identified miR-1224 as a potential survival-related miRNA in intestinal-type GC patients by The Cancer Genome Atlas (TCGA) analysis. Using quantitative real-time PCR (qRT-PCR), we showed that the relative expression of miR-1224 was significantly decreased in intestinal-type GC tissues compared to matched adjacent normal mucosa tissues (p < 0.01). We found that high miR-1224 expression was associated with no lymph-node metastasis (p < 0.05) and good prognosis (p = 0.028) in 90 intestinal-type GC tissues. Transfection of intestinal-type GC cells with miR-1224 mimics showed that miR-1224 suppressed cell migration in vitro (wound healing assay and Transwell migration assay), whereas the transfection of cells with miR-1224 inhibitor promoted cell migration in vitro. miR-1224 also suppressed intestinal-type GC cell metastasis in a xenograft mouse model. Furthermore, bioinformatics, luciferase reporter, Western blotting, and immunohistochemistry (IHC) studies demonstrated that miR-1224 directly bound to the focal adhesion kinase (FAK) gene, and downregulated its expression, which decreased STAT3 and NF-κB signaling and subsequent the epithelial-to-mesenchymal transition (EMT). Repression of FAK is required for the miR-1224-mediated inhibition of cell migration in intestinal-type GC. The present study demonstrated that miR-1224 is downregulated in intestinal-type GC. miR-1224 inhibits the metastasis of intestinal-type GC by suppressing FAK-mediated activation of the STAT3 and NF-κB pathways, and subsequent EMT. miR-1224 could represent an important prognostic factor in intestinal-type GC.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2234-943X
Relation: https://www.frontiersin.org/article/10.3389/fonc.2019.00222/full; https://doaj.org/toc/2234-943X
DOI: 10.3389/fonc.2019.00222
URL الوصول: https://doaj.org/article/e2f6169a967a499abde2ea741b135acf
رقم الانضمام: edsdoj.2f6169a967a499abde2ea741b135acf
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2234943X
DOI:10.3389/fonc.2019.00222