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Cancer Chemotherapy and Pharmacology

Erschienen in:

15.05.2021 | Original Article

MiRNA-3662 reverses the gemcitabine resistance in pancreatic cancer through regulating the tumor metabolism

verfasst von: An Liu, Yonggui Zhou, Tian Zhao, Xu Tang, Binbin Zhou, Jia Xu

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2021

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Abstract

Objectives

Gemcitabine (Gem) is one of the most commonly used chemotherapeutic drugs in treating patients with pancreatic ductal adenocarcinoma (PDAC). Acquired drug resistance against Gem presents a major clinical challenge in the chemotherapy of PDAC. It has been shown that miRNA-3662 is lowly expressed and implicated with quantities of biological processes in cancer. However, whether miRNA-3662 regulates chemoresistance in PDAC remains largely unknown.

Materials and methods

The level of miRNA-3662 in PDAC tissues was determined by real-time qPCR (RT-qPCR). Functional experiments were used to investigate the biological role of miRNA-3662 on Gem resistance of PDAC in vitro and in vivo. Fluorescence in situ hybridization (FISH), RT-qPCR, western blotting, bioinformatics analysis and luciferase reporter assay were employed to determine the precise regulation mechanisms.

Results

In this study, it was investigated that miRNA-3662 was down-regulated in PDAC clinical samples as well as cell lines. Functional assays revealed that miRNA-3662 was sufficient to inhibit Gem resistance in PDAC cells both in vitro and in vivo. Mechanistically, hypoxia-inducible factor 1ɑ (HIF-1ɑ) was one of the transcriptional target of miRNA-3662 and was up-regulated in PDAC samples. Importantly, genetic promoting of HIF-1ɑ largely compromised miR-3662-mediated chemosensitive effects. In addition, miR-3662 could impair the aerobic glycolysis in PDAC cells.

Conclusions

This study sheds light on miRNA-3662 inhibits PDAC cell chemoresistance and aerobic glycolysis through a negative feedback loop with HIF-1ɑ. Therefore, the co-delivery of miR-3662 and Gem could be served as a promising therapeutic regimen for PDAC patients.

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Titel: MiRNA-3662 reverses the gemcitabine resistance in pancreatic cancer through regulating the tumor metabolism
verfasst von: An Liu
Yonggui Zhou
Tian Zhao
Xu Tang
Binbin Zhou
Jia Xu
Publikationsdatum: 15.05.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2021
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-021-04289-z

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Springer Medizin

MiRNA-3662 reverses the gemcitabine resistance in pancreatic cancer through regulating the tumor metabolism

Abstract

Objectives

Materials and methods

Results

Conclusions

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Abstract

Objectives

Materials and methods

Results

Conclusions

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