Journal
MOLECULAR BIOTECHNOLOGY
Volume -, Issue -, Pages -Publisher
SPRINGERNATURE
DOI: 10.1007/s12033-023-00740-z
Keywords
SPINK5; EHMT2; Wnt/beta-catenin pathway; Epigenetic; Oral squamous cell carcinoma
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SPINK5 functions as a prognostic biomarker in oral squamous cell carcinoma (OSCC), and its dysregulation is related to the loss of EHMT2. SPINK5 can inhibit the aggressiveness of OSCC cells by impairing the Wnt/beta-catenin pathway. Silencing EHMT2 blocks Wnt/beta-catenin signaling and tumor growth in OSCC, which can be reversed by SPINK5 knockdown. These findings suggest that SPINK5, mediated by the loss of EHMT2, can be a potential therapeutic target for OSCC.
Serine protease inhibitor Kazal-type 5 ( SPINK5) has been revealed as a significant prognostic biomarker in oral squamous cell carcinoma (OSCC). However, there is little information regarding the detailed epigenetics mechanism underlying its dysregulation in OSCC. Using the Gene Expression Omnibus database, we identified SPINK5 as a significantly downregulated gene in OSCC tissues. Moreover, SPINK5 inhibited the malignant aggressiveness of HSC3 and squamous cell carcinomas (SCC)9 cells, whereas depletion of SPINK5 using shRNAs led to the opposite trend. The euchromatic histone lysine methyltransferase 2 (EHMT2) was found to bind to the SPINK5 promoter, and EHMT2 repressed the SPINK5 expression. SPINK5 reversed the stimulating effects of EHMT2 on the aggressiveness of HSC3 and SCC9 cells by impairing the Wnt/beta-catenin pathway. Wnt/beta-catenin inhibitor IWR-1 treatment reverted the malignant phenotype of OSCC cells in the presence of short hairpin RNA (sh)-SPINK5. Silencing of EHMT2 inhibited tumor growth and blocked the Wnt/beta-catenin signaling in OSCC, which was reversed by SPINK5 knockdown. Our study shows that SPINK5, mediated by the loss of EHMT2, can inhibit the development of OSCC by inhibiting Wnt/beta-catenin signaling and may serve as a treatment target for OSCC.
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