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Oncogenic role of MiR-130a in oral squamous cell carcinoma
Karthik Mallela1, Swamy Shivananda2, Kodaganur S Gopinath2
1Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
Abstract:
Aberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of the above pathway, regulates several cellular functions such as cell proliferation, apoptosis, migration and invasion. Downregulation of TSC1 is reported in oral as well as several other cancers and is associated with an unfavourable clinical outcome in patients. Here we show that oncogenic miR-130a binds to the 3'UTR of TSC1 and represses its expression. MiR-130a-mediated repression of TSC1 increases cell proliferation, anchorage independent growth and invasion of OSCC cells, which is dependent on the presence of the 3'UTR in TSC1. We observe an inverse correlation between the expression levels of miR-130a and TSC1 in OSCC samples, suggesting that their interaction is physiologically relevant. Delivery of antagomiR-130a to OSCC cells results in a significant decrease in xenograft size. Taken together, the findings of the study indicate that miR-130a-mediated TSC1 downregulation is not only a novel mechanism in OSCC, but also the restoration of TSC1 levels by antagomiR-130a may be a potential therapeutic strategy for the treatment of OSCC.
Insights
Oncogenic miR-130a promotes oral cancer by downregulating TSC1. Restoring TSC1 levels with antagomiR-130a offers a potential therapeutic strategy for oral squamous cell carcinoma (OSCC).
Area of Science:
- Molecular Oncology
- Cancer Biology
- MicroRNA Therapeutics
Background:
- Aberrant PI3K/AKT/mTOR pathway activation drives oral squamous cell carcinoma (OSCC) pathogenesis.
- MicroRNAs (miRNAs) are implicated in oral carcinogenesis, acting as tumor suppressors or oncogenes.
- TSC1, a pathway component, regulates cell proliferation, apoptosis, migration, and invasion; its downregulation correlates with poor prognosis in OSCC.
Purpose of the Study:
- To investigate the role of miR-130a in regulating TSC1 expression in OSCC.
- To elucidate the functional consequences of miR-130a-mediated TSC1 repression on OSCC cell behavior.
- To evaluate antagomiR-130a as a potential therapeutic agent for OSCC.
Main Methods:
- Luciferase reporter assays to confirm miR-130a binding to the TSC1 3'UTR.
- In vitro assays assessing cell proliferation, anchorage-independent growth, and invasion.
- Analysis of miR-130a and TSC1 expression correlation in OSCC patient samples.
- In vivo xenograft studies using antagomiR-130a in OSCC models.
Main Results:
- Oncogenic miR-130a directly binds to and represses TSC1 expression in OSCC cells.
- MiR-130a-induced TSC1 downregulation enhances OSCC cell proliferation, anchorage-independent growth, and invasion.
- An inverse correlation between miR-130a and TSC1 levels was observed in OSCC samples.
- AntagomiR-130a treatment significantly reduced OSCC xenograft tumor size.
Conclusions:
- MiR-130a-mediated downregulation of TSC1 is a novel mechanism contributing to OSCC development.
- Restoration of TSC1 levels via antagomiR-130a represents a promising therapeutic strategy for OSCC.
- Targeting the miR-130a/TSC1 axis holds potential for oral cancer treatment.
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