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Research article
Magnesium Isoglycyrrhizinate Suppresses the Progression of Bladder Cancer by Modulating miR-26b/Nox4 Axis
Baoping Qiao
The First Affiliated Hospital of Zhengzhou University
Corresponding Author
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Background: Magnesium Isoglycyrrhizinate (MI), a magnesium salt of 18α-GA stereoisomer, has been reported to exert efficient hepatoprotective activity. However, its effect in bladder cancer remain unclear.
Methods: The effect of MI in the growth, colony formation, apoptosis, invasion and migration of bladder cancer cells (HTB9 and BIU87 cells) was evaluated in vitro. Typical apoptotic changes of bladder cancer cells such as nuclear concentration and fragmentation was observed by Hoechst staining. The effect of MI in the expression of miR-26b, Nox4, NF-κB and HIF-1α was detected by qRT-PCR and western blot in vitro. Targetscan was used to predict the potential targets of miR-26b, then their interaction was determined by the luciferase reporter assay. Finally, the xenograft model of mice was established to evaluate the anti-tumor effects of MI in vivo.
Results: MI significantly suppressed the proliferation, colony formation, invasion, migration and induced apoptosis of human bladder cancer cells. Nox4 was identified to be a direct target of miR-26b, and MI significantly increased the expression of miR-26b. MiR-26b mimics significantly decreased the relative luciferase activity of wild type (WT) Nox4, while exhibited no obvious change in mutant type (MUT) Nox4. Meanwhile, MI markedly downregulated the expression of Nox4, NF-κB and HIF-1α both in vitro and in vivo. Moreover, MI could efficiently inhibit the growth of xenograft tumor in vivo, and also obviously decreased the expression of Nox4, NF-κB and HIF-1α.
Conclusion: In summary, MI showed a potent anti-tumor effect against bladder cancer partially through modulating miR-26b/Nox4 axis.
Keywords
Magnesium Isoglycyrrhizinate, bladder cancer, miR-26b, Nox4/ NF-κB/HIF-1α, apoptosis
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This preprint is under consideration at BMC Cancer. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Magnesium Isoglycyrrhizinate Suppresses the Progression of Bladder Cancer by Modulating miR-26b/Nox4 Axis
Baoping Qiao
The First Affiliated Hospital of Zhengzhou University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 21 Sep, 2020
No community comments so far
Review #2 received
Received 15 Dec, 2020
Editorial decision: Major revision
On 15 Dec, 2020
Reviewer #2 agreed
On 02 Dec, 2020
Review #1 received
Received 27 Sep, 2020
Reviewers invited
Invitations sent on 24 Sep, 2020
Reviewer #1 agreed
On 24 Sep, 2020
Editor assigned
On 21 Sep, 2020
Submission checks complete
On 17 Sep, 2020
Editor invited
On 17 Sep, 2020
Version (no preprint)
Posted 01 Aug, 2020
This version was not preprinted
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Magnesium Isoglycyrrhizinate (MI), a magnesium salt of 18α-GA stereoisomer, has been reported to exert efficient hepatoprotective activity. However, its effect in bladder cancer remain unclear.
Methods: The effect of MI in the growth, colony formation, apoptosis, invasion and migration of bladder cancer cells (HTB9 and BIU87 cells) was evaluated in vitro. Typical apoptotic changes of bladder cancer cells such as nuclear concentration and fragmentation was observed by Hoechst staining. The effect of MI in the expression of miR-26b, Nox4, NF-κB and HIF-1α was detected by qRT-PCR and western blot in vitro. Targetscan was used to predict the potential targets of miR-26b, then their interaction was determined by the luciferase reporter assay. Finally, the xenograft model of mice was established to evaluate the anti-tumor effects of MI in vivo.
Results: MI significantly suppressed the proliferation, colony formation, invasion, migration and induced apoptosis of human bladder cancer cells. Nox4 was identified to be a direct target of miR-26b, and MI significantly increased the expression of miR-26b. MiR-26b mimics significantly decreased the relative luciferase activity of wild type (WT) Nox4, while exhibited no obvious change in mutant type (MUT) Nox4. Meanwhile, MI markedly downregulated the expression of Nox4, NF-κB and HIF-1α both in vitro and in vivo. Moreover, MI could efficiently inhibit the growth of xenograft tumor in vivo, and also obviously decreased the expression of Nox4, NF-κB and HIF-1α.
Conclusion: In summary, MI showed a potent anti-tumor effect against bladder cancer partially through modulating miR-26b/Nox4 axis.
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