MICRORNA-222 AND MICRORNA-203 SIGNATURES IN ORAL SQUAMOUS CELL CARCINOMA: POTENTIAL ROLE IN PROGRESSION AND AS THERAPEUTIC TARGETS

Abstract

Objectives To discuss the proposed role of microRNA-222 (miR-222) and microRNA-203 (miR-203) in oral squamous cell carcinoma in the progression and as possible therapeutic targets. Findings miR-222 is colocalized as a cluster in the short arm of chromosome X. Luciferase reporter gene assays in oral tongue squamous cell carcinoma (OTSCC) have shown that hsa-miR-222 regulates the MMP1 expression through both direct cis-regulatory mechanism (targeting MMP1 mRNA) and indirect trans-regulatory mechanism (indirect controlling of MMP1 gene expression by targeting SOD2). Hence, hsa-miR-222 might serve as a novel therapeutic target for OTSCC patients at risk of metastatic disease. miR-222 has been shown to regulate TRAIL resistance and enhancement of tumorigenicity through PTEN and TIMP3(Tissue inhibitor of metalloproteinase 3) downregulation. miR-222 has been implicated to target PUMA(p53 up-regulated modulator of apoptosis) to improve sensitization of UM1 cells to Cisplatin. miR-203 acts as a molecular switch between keratinocyte proliferation and differentiation in adult epidermis by targeting ΔNp63 mRNA. Following DNA damage, ΔNp63 downregulates and a possible activation of the apoptotic program in head and neck squamous cell carcinoma has been thought of. miR-203 has been shown to target EIF5A2 in colorectal cancer cells. Serving as a tumor suppressor gene, miR-203 has been thought to be a useful potential therapeutic target in colorectal cancer. miR-203 as a therapeutic target in oral squamous cell carcinoma needs further validation. Conclusion In tumour progression, several cellular pathways may be affected by a single microRNA since it can target multiple mRNAs. Much more light is to be shed by developing as well as by tracking the identified microRNA signatures in oral squamous cell carcinoma, to pave the way for their future clinical use in the diagnosis, management, and prognosis.