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Updated: Nov 21, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MicroRNA-21 Contributes to Cutaneous Squamous Cell Carcinoma Progression via Mediating TIMP3/PI3K/AKT Signaling Axis
1Department of Dermatology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161000, People's Republic of China.
Background:
Though the therapeutic potentials of microRNAs (miRNAs) are extensively explored in cutaneous squamous cell carcinoma (CSCC), the concrete function of miR-21 in this disorder has not been thoroughly comprehended. Therein, this work is launched to clarify the miR-21-pivoted mechanism in CSCC from the perspective of tissue inhibitor of metalloproteinases-3 (TIMP3) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.
Methods:
Microarray-based analysis was utilized to screen out miR-21 with the most up-regulated expression in CSCC tissues. The relation between miR-21 and TIMP3 expression in tissues, and the overall survival of CSCC patients was evaluated. Loss-of-function assays were performed in cells to explore the independent and combined functions of miR-21 and TIMP3 in CSCC cell progression. Mice were injected with miR-21 inhibitor or TIMP3 si for identifying their roles in tumor formation and liver metastasis. The mechanism among miR-21, TIMP3 and PI3K/AKT pathway was interpreted.
Results:
MiR-21 was up-regulated while TIMP3 was down-regulated in CSCC tissues, which were connected with unsatisfactory survival of patients. Down-regulating miR-21 inhibited CSCC cell progression and retarded CSCC tumor formation and metastasis in mice. Silencing of TIMP3 reversed the effects of miR-21 down-regulation on CSCC progression. Besides, down-regulating miR-21 inhibited PI3K/AKT pathway activation in CSCC cells via mediating TIMP3.
Conclusion:
It is elucidated that miR-21 depletion impedes CSCC cell invasion and metastasis via enhancing TIMP3 and suppressing PI3K/AKT pathway activation.
Insights
Down-regulating miR-21 inhibits cutaneous squamous cell carcinoma (CSCC) progression by increasing tissue inhibitor of metalloproteinases-3 (TIMP3) and reducing PI3K/AKT pathway activation. This finding clarifies miR-21's role in CSCC development and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) show therapeutic potential in cutaneous squamous cell carcinoma (CSCC).
- The precise function of miR-21 in CSCC remains unclear.
- This study investigates the miR-21 mechanism involving tissue inhibitor of metalloproteinases-3 (TIMP3) and the PI3K/AKT pathway in CSCC.
Purpose of the Study:
- To elucidate the role of miR-21 in CSCC.
- To investigate the regulatory relationship between miR-21, TIMP3, and the PI3K/AKT pathway in CSCC.
- To explore therapeutic strategies targeting miR-21 for CSCC treatment.
Main Methods:
- Microarray analysis identified up-regulated miR-21 in CSCC tissues.
- Correlation analysis assessed the relationship between miR-21, TIMP3, and patient survival.
- Loss-of-function assays and in vivo studies (mice) evaluated the impact of miR-21 and TIMP3 modulation on CSCC progression, tumor formation, and metastasis.
Main Results:
- MiR-21 was significantly up-regulated, and TIMP3 was down-regulated in CSCC tissues, correlating with poor patient survival.
- Down-regulation of miR-21 inhibited CSCC cell progression, tumor formation, and metastasis in mice.
- TIMP3 silencing reversed the inhibitory effects of miR-21 down-regulation.
- Reduced miR-21 suppressed PI3K/AKT pathway activation in CSCC cells by modulating TIMP3.
Conclusions:
- MiR-21 depletion hinders CSCC cell invasion and metastasis.
- This effect is mediated by enhanced TIMP3 expression and suppressed PI3K/AKT pathway activation.
- Targeting miR-21 offers a potential therapeutic strategy for CSCC.
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