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MicroRNA-7 overexpression positively regulates the CD8+ SP cell development via targeting PIK3R1
1Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Guizhou, 563000, China; Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Guizhou, 563000, China.
Abstract:
microRNA-7 (miR-7), a distinct miRNA family member, has been reported to be involved in the biological functions of immune cells. However, the potential role of miR-7 in the CD8+ T cell development remains to be elucidated. In this study, we estimated the potential effects of miR-7 overexpression in the thymic CD8+ SP cell development using miR-7 overexpression mice. Our results showed that compared with those in control wild type (WT) mice, the volume, weight and total cell numbers of thymus in miR-7 overexpression (OE) mice increased significantly. The absolute cell number of CD8+ SP cells in miR-7 OE mice increased and its ability of activation and proliferation enhanced. Futhermore, we clarified that miR-7 overexpression had an intrinsic promote role in CD8+ SP cell development by adoptive cell transfer assay. Mechanistically, the expression level of PIK3R1, a target of miR-7, decreased significantly in CD8+ SP cells of miR-7 OE mice. Moreover, the expression level of phosphorylated (p)-AKT and p-ERK changed inversely and indicating that miR-7 overexpression impaired the balance of AKE and ERK pathways. In summary, our work reveals an essential role of miR-7 in promoting CD8+ SP cell development through the regulation of PIK3R1 and balance of AKT and ERK pathways.
Insights
MicroRNA-7 (miR-7) promotes CD8+ T cell development by regulating PIK3R1 and balancing AKT/ERK pathways. Overexpression of miR-7 enhances thymus size and CD8+ T cell activation and proliferation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- MicroRNA-7 (miR-7) is implicated in immune cell functions.
- The specific role of miR-7 in CD8+ T cell development is largely unknown.
Purpose of the Study:
- To investigate the effects of miR-7 overexpression on thymic CD8+ T cell development.
- To elucidate the underlying molecular mechanisms.
Main Methods:
- Utilized miR-7 overexpression mice models.
- Performed adoptive cell transfer assays.
- Analyzed thymus volume, weight, cell numbers, and expression of key signaling molecules (PIK3R1, p-AKT, p-ERK).
Main Results:
- miR-7 overexpression significantly increased thymus size and total cell numbers.
- Absolute CD8+ T cell numbers, activation, and proliferation were enhanced in miR-7 overexpressing mice.
- PIK3R1 expression decreased, while p-AKT and p-ERK levels showed inverse changes, indicating pathway imbalance.
Conclusions:
- miR-7 plays a crucial role in promoting CD8+ T cell development.
- This promotion is mediated by the downregulation of PIK3R1 and the modulation of AKT and ERK signaling pathways.
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