Zheng Jie, Liu Yuzhen, Qiao Yanchun, Zhang Liying, Lu Shijun
Department of Diagnostic Pathology, Weifang Medical University, Weifang 261053, China.
Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang 261053, China.
Int J Mol Sci. 2017 Apr 26;18(5):910. doi: 10.3390/ijms18050910.
MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed to confirm clinical significance of miR-103 and investigate its biological role and underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103 was highly expressed in GC tissues and cell lines. miR-103 expression was correlated closely with tumor size, Lauren's classification, and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of miR-103 was significantly associated with poor overall survival and disease-free survival of GC patients. Downregulation of miR-103 by transfecting with miR-103 inhibitor significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target databases and luciferase reporter assay confirmed that Krüppel-like Factor-4 () was a direct target of miR-103 in GC, and there was a significant inverse correlation between miR-103 and expression in GC tissues. Moreover, downregulation could rescue miR-103's oncogenic effect on GC cell proliferation, apoptosis, migration, and invasion. Therefore, these results suggested that miR-103 overexpression could contribute to tumor progression by suppressing , and it might serve as a promising candidate for the prognosis of GC patients.
微小RNA(miRNA)在癌症的发生和发展中发挥着重要作用;已在多种肿瘤中发现miR-103过表达。然而,其在人类胃癌(GC)调控中的生物学功能和调控机制仍 largely 未知。本研究旨在证实miR-103的临床意义,并研究其在GC中的生物学作用及潜在机制。实时定量聚合酶链反应(qRT-PCR)显示miR-103在GC组织和细胞系中高表达。miR-103表达与肿瘤大小、Lauren分类及淋巴结转移密切相关。重要的是,Kaplan-Meier分析显示miR-103高表达与GC患者的总生存期和无病生存期显著相关。通过转染miR-103抑制剂下调miR-103可在体内外显著抑制细胞增殖、诱导凋亡、抑制迁移和侵袭。此外,miRNA靶标数据库和荧光素酶报告基因检测证实Krüppel样因子4()是GC中miR-103的直接靶标,且GC组织中miR-103与表达之间存在显著负相关。此外,下调可挽救miR-103对GC细胞增殖、凋亡、迁移和侵袭的致癌作用。因此,这些结果表明miR-103过表达可能通过抑制促进肿瘤进展,它可能是GC患者预后的一个有前景的候选指标。 (注:原文中“Krüppel-like Factor-4 ()”括号内内容缺失,翻译时保留原文形式)