肿瘤抑制microRNA-551b-3p靶向H6PD抑制胆囊癌进展
Tumor-suppressive microRNA-551b-3p targets H6PD to inhibit gallbladder cancer progression
原文发布日期:2020-11-29
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Gallbladder cancer (GBC) is a highly malignant cancer with poor prognosis. Extensive studies have reported the vital functionality of several microRNAs (miRNAs) in numerous human cancers, including GBC. Microarray analysis has identified the differentially expressed miR-551b-3p in GBC. Therefore, this study aims to validate the underlying mechanism by which miR-551b-3p participated in epithelial–mesenchymal transition (EMT), invasion and migration of GBCs. Bioinformatic analysis predicted the binding of miR-551b-3p to H6PD. We validated the reduced miR-551b-3p expression and increased H6PD expression in the GBC tissues and GBC cell lines. Artificial modulation of miR-551b-3p and H6PD (down- and upregulation) was conducted to explore their roles in EMT, invasive, and migratory abilities of GBCs, and the tumor-bearing mice were used to determine tumor growth. Overexpression of miR-551b-3p or silencing of H6PD was observed to suppress the expressions of N-cadherin and vimentin, and to promote the expression of E-cadherin, along with reduced invasive and migratory ability of GBCs. Mechanistically, miR-551b-3p could evidently target and inhibit the expression of H6PD. Moreover, in vivo experiments substantiated the tumor-inhibiting activities of miR-551b-3p in nude mice. Conjointly, our study suggests that overexpression of miR-551b-3p inhibited the EMT, migration, and invasion of GBCs by inhibiting the expression of H6PD, indicating that miR-551b-3p may serve as a potential target for future development of therapeutic strategies for GBC.
胆囊癌(GBC)是一种恶性程度高且预后较差的癌症。大量研究报道了多种microRNA(miRNA)在包括GBC在内的多种人类癌症中的重要作用。微阵列分析发现miR-551b-3p在GBC中存在差异性表达。因此,本研究旨在验证miR-551b-3p参与GBC上皮间质转化(EMT)、侵袭和迁移的潜在机制。生物信息学分析预测miR-551b-3p可与H6PD结合。我们证实了GBC组织和GBC细胞系中miR-551b-3p表达降低而H6PD表达升高。通过人工调控miR-551b-3p和H6PD(下调和上调)来探索它们在GBC的EMT、侵袭和迁移能力中的作用,并使用荷瘤小鼠检测肿瘤生长。研究发现过表达miR-551b-3p或沉默H6PD可抑制N-钙黏蛋白和波形蛋白的表达,并促进E-钙黏蛋白的表达,同时降低GBC的侵袭和迁移能力。从机制上讲,miR-551b-3p能够明显靶向并抑制H6PD的表达。此外,体内实验证实了miR-551b-3p在裸鼠中的肿瘤抑制活性。我们的研究表明,过表达miR-551b-3p通过抑制H6PD的表达来抑制GBC的EMT、迁移和侵袭,表明miR-551b-3p可能作为未来开发GBC治疗策略的潜在靶点。
Tumor-suppressive microRNA-551b-3p targets H6PD to inhibit gallbladder cancer progression
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