MIRNA193A INHIBITS HEAD AND NECK CANCER CELL GROTH: EVIDENCE FROM CELL AND XENOGRAFT MODELS

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to messenger RNA (mRNA) and inhibiting its translation. As epigenetic mechanisms, their effects are potentially reversible, making them attractive targets for therapeutic intervention. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide and is associated with high mortality and poor prognosis.

In this study, we found that the promoter region of miR-193a is highly methylated in FaDu HNSCC cells, suggesting epigenetic silencing of its expression. Consistently, miR-193a levels were undetectable in tumor biopsies from HNSCC patients. Reactivation of miR-193a, either by treatment with a DNA methyltransferase inhibitor or via transduction with miR-193a, significantly reduced cell viability in a dose- and time-dependent manner and induced apoptosis via the intrinsic caspase pathway.

To further investigate its function, we cloned miR-193a into an adenoviral expression vector (Ad-miR-193a) for both in vitro and in vivo studies. Overexpression of miR-193a in HNSCC cells led to marked inhibition of cell growth and activation of apoptosis. In xenograft mouse models, Ad-miR-193a treatment significantly suppressed tumor development. Mechanistically, miR-193a inactivated the AKT/mTOR signaling pathway by downregulating key components, including PIK3R3, mTOR, S6KB2, and ERBB4.

These findings demonstrate that miR-193a functions as a tumor suppressor in HNSCC and plays a critical role in tumor progression. Thus, miR-193a holds promise as both a diagnostic biomarker and a potential therapeutic agent in head and neck cancer.