MicroRNA-19b-3p suppresses gastric cancer development by negatively regulating neuropilin-1
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PRIMARY RESEARCH
Cancer Cell International Open Access
MicroRNA‑19b‑3p suppresses gastric cancer development by negatively regulating neuropilin‑1 Yingfeng Wei1† , Sheng Guo2†, Jianhua Tang1, Jianjun Wen1, Huifen Wang3, Xiaobo Hu3* and Qiuping Gu1*
Abstract Background: Gastric cancer (GC) remains one of the most common digestive malignancies worldwide and ranked third causes of cancer-related death. Mounting evidence has revealed that miRNAs exert critical regulatory roles in GC development. Methods: Immunohistochemistry (IHC) and western blot assay were performed to determine the protein expression levels of neuropilin-1 (NRP1) and mRNA levels were confirmed by quantitative RT-PCR (qRT-PCR) in GC tissues. Kaplan– Meier analysis was performed to evaluate the prognostic value of NRP1 in GC. Knockdown of NRP1 was conducted to analyse its function in vitro and vivo. Luciferase reporter assay, western blot and qRT-qPCR were employed to identify the miRNAs which directly targeted NRP1. Furthermore, Bioinformatics analysis and experimental verification were used to explore the potential molecular mechanism and signalling pathway. Results: In the current study, we revealed that NRP1 was highly expressed in GC tumor tissues and was associated with poor prognosis in GC patients. NRP1 knockdown inhibited GC cell growth, migration and invasion in vitro, while suppressed GC xenograft tumor development in vivo. Bioinformatics analysis predicted that miR-19b-3p downregulated NRP1 expression by targeting its 3′-UTR. Functional assay demonstrated that miR-19b-3p inhibited GC cell growth, migration and invasion via negatively regulating NRP1. Overexpression NRP1 partially reversed the regulatory effect of miR-19b-3p. Moreover, we showed that miR-19b-3p/NRP1 axis regulated the epithelial-to-mesenchymal transition and focal adhesion in GC, which might contribute the GC development and progression. Conclusions: Taken together, our findings suggest a regulatory network of miR-19b-3p/NRP1 in GC development. The miR-19b-3p/NRP1 axis might be further explored as a potential diagnostic and therapeutic target in GC. Keywords: Gastric cancer, NRP1, miR-19b-3p Background Gastric cancer (GC) remains one of the most common digestive malignancies worldwide and ranked third causes of cancer-related death [1]. Technical advances *Correspondence: [email protected]; [email protected] † Yingfeng Wei, Sheng Guo contributed equally to this work 1 Department of Gastroenterology, Ganzhou People’s Hospital, Ganzhou, Jiangxi 341000, China 3 Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China Full list of author information is available at the end of the article
in the past decades greatly improve the diagnosis and treatment of GC, however, the prognosis remains poor as most GC patients are diagnosed at relative advanced stages [2, 3]. The lack of initial symptoms in GC patients and acquired resistant to anti-cancer drugs results in the low 5-year overall survival rate [4]. Thus, the i
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