miR-324-5p inhibits gallbladder carcinoma cell metastatic behaviours by downregulation of transforming growth factor beta 2 expression

被引:26
作者
Zhang, Xinrong [1 ]
Zhang, Lei [2 ]
Chen, Ming [3 ]
Liu, Dongying [4 ]
机构
[1] Tianjin Nankai Hosp, Dept Digest Med, Tianjin, Peoples R China
[2] Civil Affairs Bur Tianjin, Geriatr Hosp, Dept Tradit Chinese Med, Tianjin, Peoples R China
[3] Tianjin Nankai Hosp, Dept Liver Tumor Internal Med, 6 Changjiang Rd, Tianjin 300100, Peoples R China
[4] Tianjin Med Univ Canc Inst & Hosp, Dept Integrated Tradit Chinese & Western Med, Tianjin, Peoples R China
关键词
miR-324-5p; GBC; metastasis; behaviours; TGFB2; CANCER STATISTICS; PANCREATIC-CANCER; TUMOR-SUPPRESSOR; GLIOMA; PROLIFERATION; MICRORNAS; PATHWAY;
D O I
10.1080/21691401.2019.1703724
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Increasing studies have demonstrated that microRNAs (miRNAs) are associated with the metastasis of gallbladder carcinoma (GBC). Recently, miR-324-5p has been reported to be a tumour-suppressive miRNA in many types of malignant cancer. However, the biological function and molecular mechanism of miR-324-5p in GBC still remain largely unknown. Here, we found that miR-324-5p expression was notably down-regulated in both GBC tissues and cells compared with that in normal controls. Downregulated miR-324-5p expression was negatively associated with the status of local invasion and lymph node metastasis and predicted a poor prognosis in GBC patients. Further functional assays revealed that restoration of miR-324-5p significantly suppressed GBC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and impeded the metastasis of GBC cells in vivo. Moreover, RNA immunoprecipitation (RIP) and dual-luciferase reporter assay confirmed that the transforming growth factor beta 2 (TGFB2) was a direct target gene of miR-324-5p in GBC cells. Mechanically, small interfering RNA (siRNA)-mediated knockdown of TGFB2 partially phenocopied the inhibitory effects of miR-324-5p overexpression on GBC cell metastatic phenotypes. In summary, our findings demonstrated that miR-324-5p targets TGFB2 expression to inhibit GBC cell metastatic behaviors, and implying miR-324-5p as a potential biomarker for diagnostic and therapeutic strategies in GBC.
引用
收藏
页码:315 / 324
页数:10
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