Tumor-suppressive microRNA-551b-3p targets H6PD to inhibit gallbladder cancer progression

Abstract

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.

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Fig. 1: MiR-551b-3p is involved in the regulation of GBCs by monitoring H6PD expression.
Fig. 2: miR-551b-3p expresses lower while H6PD expresses higher in GBC tissues and cells than in chronic cholecystitis tissues and HGBECs.
Fig. 3: miR-551b-3p overexpression inhibits EMT of GBCs.
Fig. 4: miR-551b-3p negatively inhibits H6PD expression.
Fig. 5: H6PD silencing inhibits EMT, invasion, and migration of GBCs.
Fig. 6: Inhibition of EMT, migration, and invasion of GBCs through upregulation of miR-551b-3p could be reversed by upregulating H6PD expression in vitro.
Fig. 7: Inhibition of EMT, migration, and invasion of GBCs through upregulation of miR-551b-3p could be reversed by upregulating H6PD expression in vivo.
Fig. 8: Mechanism hypothesis diagram.

Data availability

The data sets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We give our sincere gratitude to the reviewers for their valuable suggestions.

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Tao Ji, Lijun Gao, and Zongbu Yu wrote the main manuscript text, Tao Ji collected the data, and Lijun Gao prepared all tables. All authors reviewed the manuscript.

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Correspondence to Zongbu Yu.

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Ji, T., Gao, L. & Yu, Z. Tumor-suppressive microRNA-551b-3p targets H6PD to inhibit gallbladder cancer progression. Cancer Gene Ther (2020). https://doi.org/10.1038/s41417-020-00252-x

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