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Updated: Jul 29, 2025
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MiR-3960 inhibits bladder cancer progression via targeting of DEXI
Wenqing Li1, Zihao Wang2, Ziming Jiang2
1Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Purpose:
MicroRNAs (miRNAs) are dominant cargo in exosomes and act as master regulators of cell function, inhibiting mRNA translation and affecting gene silencing. Some aspects of tissue-specific miRNA transport in bladder cancer (BC) and its role in cancer progression are not fully understood.
Materials And Methods:
A microarray was used to identify miRNAs in mouse bladder carcinoma cell line MB49 exosomes. Real-time reverse transcription polymerase chain reaction was used to examine the expression of miRNAs in BC and healthy donor serum. Western blotting and immunohistochemical staining were used to examine the expression of dexamethasone-induced protein (DEXI) in patients with BC. CRISPR-Cas 9 was used to knock out Dexi in MB49, and flow cytometry was performed to test cell proliferation ability and apoptosis under chemotherapy. Human BC organoid culture, miR-3960 transfection, and 293T-exosome-loaded miR-3960 delivery were used to analyze the effect of miR-3960 on BC progression.
Results:
The results showed that miR-3960 levels in BC tissue were positively correlated with patient survival time. Dexi was a major target of miR-3960. Dexi knockout inhibited MB49 cell proliferation and promoted cisplatin- and gemcitabine-induced apoptosis. Transfection of miR-3960 mimic inhibited DEXI expression and organoid growth. In parallel, 293T-exosome-loaded miR-3960 delivery and Dexi knockout significantly inhibited subcutaneous growth of MB49 cells in vivo.
Conclusion:
Our results demonstrate the potential role of miR-3960-mediated inhibition of DEXI as a therapeutic strategy against BC.
Insights
MicroRNA-3960 (miR-3960) targets DEXI, inhibiting bladder cancer progression. Exosomes delivering miR-3960 and DEXI knockout show therapeutic potential against bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression, often transported via exosomes.
- The role of specific miRNAs in bladder cancer (BC) progression and exosomal transport remains incompletely understood.
Purpose of the Study:
- To investigate the role of miR-3960 in bladder cancer (BC) progression.
- To identify the target of miR-3960 and its therapeutic potential in BC.
Main Methods:
- Microarray analysis identified miRNAs in mouse bladder carcinoma exosomes.
- Real-time RT-PCR, Western blotting, and immunohistochemistry assessed miRNA and DEXI expression.
- CRISPR-Cas9 gene editing, organoid culture, and in vivo xenografts evaluated miR-3960 and DEXI function.
Main Results:
- miR-3960 levels correlated positively with survival in BC patients.
- DEXI was identified as a direct target of miR-3960.
- miR-3960 inhibition of DEXI suppressed BC cell proliferation, enhanced chemotherapy-induced apoptosis, and reduced tumor growth in vitro and in vivo.
Conclusions:
- miR-3960 plays a critical role in regulating bladder cancer progression.
- Targeting the miR-3960/DEXI axis presents a promising therapeutic strategy for bladder cancer.
