Expression profile of miR-99a and miR-218 across oral submucous fibrosis and oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) remains a major public health concern in India, often preceded by Oral Submucous Fibrosis (OSMF), a chronic progressive condition with malignant potential. MicroRNAs (miRNAs), including miR-99a and miR-218, are critical post-transcriptional regulators implicated in tumorigenesis and fibrosis. However, limited studies have assessed their expression profiles across the OSCC–OSMF continuum, particularly in Indian cohorts. This study investigates the expression patterns of miR-99a and miR-218 and their correlation with clinical and histopathological variables. Materials and Methods: FFPE tissue samples from 15 OSCC patients, 15 OSMF patients and 10 healthy controls were analysed. Sections were deparaffinized and total RNA was extracted with DNase treatment. Reverse transcription and SYBR Green-based qRT-PCR were performed to quantify miR-99a and miR-218 expression. Ct values were normalized to U6 snRNA and fold changes were calculated using the 2^ (- ΔΔ Ct) method. Statistical analyses included Kruskal-Wallis test and Dunn’s post hoc test, with significance set at P < 0.05. Results: miR-99a was significantly downregulated in OSCC (mean Ct: 29.3 ± 1.4) and OSMF (mean Ct: 28.4 ± 1.1) compared with normal mucosa (mean Ct: 26.1 ± 1.5; P = 0.002). miR-218 expression was elevated in OSMF (mean Ct: 27.7 ± 1.3) and OSCC (mean Ct: 28.1 ± 1.5) versus normal (mean Ct: 29.9 ± 1.2; P = 0.004). Both miRNAs showed significant correlations with age, gender, lesion site, histological grade (in OSCC) and fibrosis stage (in OSMF). Conclusion: Distinct expression patterns of miR-99a and miR-218 across OSCC and OSMF suggest their roles in regulating epithelial dysplasia, fibrosis and tumor progression. These miRNAs hold promise as minimally invasive biomarkers for early diagnosis, prognosis and personalized therapeutic targeting in oral potentially malignant and malignant disorders.