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Updated: May 1, 2026

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Mir-302 cluster exhibits tumor suppressor properties on human unrestricted somatic stem cells
Fatemeh Jamshidi-Adegani1, Lida Langroudi, Abbas Shafiee
1Department of Molecular Medicine, Qazvin University of Medical Science, Qazvin, Iran.
Abstract:
Many studies have reported that miR-302-367 cluster acts in different ways in various cell types. For instance, this cluster is shown to have a potential role in stemness regulation in embryonic stem cells (ESCs). On the other hand, this cluster inhibits the tumorigenicity of human pluripotent stem cells by coordinated suppression of CDK2 and CDK4/6 cell cycle pathways. Indeed, this cluster has a significant posttranscriptional impact on cell cycle progression. Previous reports have shown the participation of miR-302-367 cluster in cell cycle regulation of hESCs, MCF7, HepG2, and Teta-2 embryonal teratocarcinoma cells, but its effect on unrestricted somatic stem cells (USSCs) as a new source of human somatic stem cells from the umbilical cord blood remains to be elucidated. Therefore, in this study, we aimed to investigate the effect of miR-302-367 cluster on cell proliferation by MTT assay, cell cycle analysis, and colony formation assay. In addition, the expression of candidate cell cycle regulatory performance and tumor suppressor genes was determined. In this study, for the first time, we found that miR-302-367 cluster not only did not reprogram human USSCs into a pluripotent ESC-like state, but also inhibited the proliferation of human USSCs. Moreover, analyzing the cell cycle curve revealed a significant apoptotic phase upon viral introduction of miR-302-367. Our gene expression study revealed the overexpression of candidate genes after transduction of USSCs with miR-302-367 cluster. In conclusion, the controversial role of miR-302-367 in different cell types may provide better understanding for its role in stemness level and its antitumorigenicity potential in different contexts.
Insights
The miR-302-367 cluster, previously linked to stemness and tumor suppression, was found to inhibit proliferation and induce apoptosis in unrestricted somatic stem cells (USSCs). This study clarifies its complex role in different cell types.
Area of Science:
- Molecular Biology
- Stem Cell Biology
- Cancer Research
Background:
- The miR-302-367 cluster exhibits varied functions across cell types, including stemness regulation in embryonic stem cells (ESCs) and inhibition of tumorigenicity in pluripotent stem cells.
- While its role in cell cycle regulation is documented in several cell lines, its impact on unrestricted somatic stem cells (USSCs) remains unexplored.
Purpose of the Study:
- To investigate the effect of the miR-302-367 cluster on the proliferation and cell cycle progression of human USSCs.
- To determine the expression of cell cycle regulatory and tumor suppressor genes following miR-302-367 cluster introduction.
Main Methods:
- MTT assay for cell proliferation.
- Cell cycle analysis.
- Colony formation assay.
- Gene expression analysis of candidate cell cycle regulators and tumor suppressors.
Main Results:
- The miR-302-367 cluster did not reprogram USSCs into an ESC-like state.
- Introduction of the miR-302-367 cluster inhibited USSC proliferation and induced a significant apoptotic phase.
- Gene expression analysis revealed overexpression of specific candidate genes after miR-302-367 cluster transduction.
Conclusions:
- The miR-302-367 cluster inhibits proliferation and induces apoptosis in human USSCs, contrasting with its roles in other cell types.
- These findings highlight the context-dependent functions of miR-302-367, contributing to understanding its stemness and antitumorigenicity potential.
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