miRNA regulation of the Akt/mTOR pathway in oral squamous cell carcinoma: a focused review

Abstract

Oral squamous cell carcinoma (OSCC) contributes significantly to global cancer mortality, characterized by a progression from hyperplasia to invasive cancer through a series of genetic and epigenetic alterations. Central to this progression is the Akt/mTOR signaling pathway, which regulates cell proliferation and survival. This review examines the role of microRNAs (miRNAs) in modulating the Akt/mTOR pathway and their implications for OSCC. The Akt/mTOR pathway, activated by receptor tyrosine kinases and involving the PI3K/AKT/mTOR complexes, is crucial for tumor cell growth and metabolism. Dysregulation of this pathway is frequently observed in OSCC, leading to increased proliferation, survival, and metastasis. miRNAs, such as miR-21, miR-99, and miR-145, play significant roles in regulating this pathway by influencing key components like Akt and mTOR. These miRNAs can act as oncogenes or tumor suppressors, affecting cancer progression and response to therapy. The review highlights the potential of targeting miRNAs for OSCC treatment, including strategies to restore normal miRNA levels or inhibit aberrant miRNAs. Such targeted therapies offer promise for improving treatment outcomes and overcoming drug resistance in OSCC.

Keywords: Akt/mTOR signaling pathway; Biomarkers; Cancer metastasis; Cell proliferation; Epigenetic modifications; Genetic alterations; MicroRNAs; Oral squamous cell carcinoma; Therapeutic targets.

Fig. 1

Schematic representation of the EGFR-Akt/mTOR signaling cascade and its regulation by key miRNAs in OSCC. miR-21 and miR-155 promote tumorigenic signaling by downregulating PTEN and enhancing PI3K/Akt activation, while miR-34a exerts tumor-suppressive effects by targeting SIRT1 and Bcl-2. These miRNAs collectively modulate critical nodes within the pathway, influencing cell survival, proliferation, and metastatic potential