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The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer
H Yoshino1, T Chiyomaru, H Enokida
1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Background:
On the base of the microRNA (miRNA) expression signature of bladder cancer (BC), we found that miR-1 and miR-133a were significantly downregulated in BC. In this study, we focussed on the functional significance of miR-1 and miR-133a in BC cell lines and identified a molecular network of these miRNAs.
Methods And Results:
We investigated the miRNA expression signature of BC clinical specimens and identified several downregulated miRNAs (miR-133a, miR-204, miR-1, miR-139-5p, and miR-370). MiR-1 and miR-133a showed potential role of tumour suppressors by functional analyses of BC cells such as cell proliferation, apoptosis, migration, and invasion assays. Molecular target searches of these miRNAs showed that transgelin 2 (TAGLN2) was directly regulated by both miR-1 and miR-133a. Silencing of TAGLN2 study demonstrated significant inhibitions of cell proliferation and increase of apoptosis in BC cell lines. The immunohistochemistry showed a positive correlation between TAGLN2 expression and tumour grade in clinical BC specimens.
Conclusions:
The downregulation of miR-1 and miR-133a was a frequent event in BC, and these miRNAs were recognised as tumour suppressive. TAGLN2 may be a target of both miRNAs and had a potential oncogenic function. Therefore, novel molecular networks provided by miRNAs may provide new insights into the underlying molecular mechanisms of BC.
Insights
MicroRNA (miRNA) expression signatures reveal miR-1 and miR-133a are downregulated in bladder cancer (BC), acting as tumor suppressors. Their target, TAGLN2, promotes BC progression, offering new therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer (BC) exhibits altered microRNA (miRNA) expression profiles.
- Specific miRNAs, including miR-1 and miR-133a, are significantly downregulated in BC.
- This downregulation suggests a potential role in BC pathogenesis.
Purpose of the Study:
- To investigate the functional significance of miR-1 and miR-133a in BC.
- To identify the molecular network regulated by these miRNAs.
- To explore the potential of these miRNAs as therapeutic targets in BC.
Main Methods:
- Analysis of miRNA expression signatures in BC clinical specimens.
- Functional assays in BC cell lines (proliferation, apoptosis, migration, invasion).
- Identification of miRNA targets using molecular search tools and validation through gene silencing and immunohistochemistry.
Main Results:
- miR-1 and miR-133a were found to be downregulated in BC.
- Functional analyses indicated miR-1 and miR-133a act as tumor suppressors.
- Transgelin 2 (TAGLN2) was identified as a direct target of both miR-1 and miR-133a.
- TAGLN2 silencing inhibited BC cell proliferation and increased apoptosis.
- TAGLN2 expression positively correlated with tumor grade in BC specimens.
Conclusions:
- Downregulation of miR-1 and miR-133a is common in BC and they function as tumor suppressors.
- TAGLN2, a target of these miRNAs, exhibits oncogenic properties.
- MiRNA-mediated molecular networks offer novel insights into BC mechanisms.
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