MicroRNA-146a-5p Regulates Inflammation in Inflamed OECM-1 Cells: Implications for Periodontal Disease

Pin-Si Yin^1,#, Chang-Chin Wu^1,2,#, Shih-Yuan Chiu¹, Karina Erda Saninggar³, Ardianti Maartrina Dewi³, Kai-Chiang Yang^1,3,4,*
1 School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
2 Department of Orthopedics, En Chu Kong Hospital, New Taipei City, Taiwan
3 Department of Pediatric Dentistry, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
4 Orthopedics Research Center, Taipei Medical University Hospital, Taipei, Taiwan
* Corresponding Author: Kai-Chiang Yang. Email: email
# These authors contributed equally to this work
(This article belongs to the Special Issue: Unraveling Periodontal Disease: Molecular and Cellular Perspectives)

BIOCELL https://doi.org/10.32604/biocell.2026.081934

Received 11 March 2026; Accepted 08 July 2026; Published online 23 July 2026

Abstract

Objective: Periodontal diseases can cause pro-inflammatory cytokine overproduction, particularly tumor necrosis factor-alpha (TNF-α), and this inflammatory microenvironment is a critical driver of oral cancer progression. MicroRNA-146a-5p is a key regulator of inflammation, linked to both periodontal disease and carcinogenesis. The objective of this study was to illustrate the regulatory function of miR-146a-5p in gingival squamous cell carcinoma OECM-1 cells under conditions that mimic those of periodontal disease. Methods: OECM-1 cells were stimulated with 25 ng/mL TNF-α for 48 h, and subsequently transfected with 50 nM miR-146a-5p mimic or inhibitor for an additional 48 h. The inflammatory extracellular matrix components were demonstrated, and wound closure, cell invasion, and colony formation were evaluated to investigate cell motility in treated cells. Results: Overexpression of miR-146a-5p significantly downregulated mRNA levels of TNFA (p < 0.05), IL1B (p < 0.01), IL6 (p < 0.01), and IL8 (p < 0.05) while increasing IL6R (p < 0.001) and COL4A1 (p < 0.05) in stimulated cells. TNF-α stimulation also increased cortactin (p < 0.05) and coronin-1B (p < 0.01) mRNA levels, which may influence cellular migration and invasion dynamics. The results from the inflammatory protein array indicated that transfection with a miR-146a-5p mimic reduced the secretion of interleukin 6 (IL-6), IL-6sR, and IL-8. Conversely, the observed increase in TIMP-2 may contribute to matrix remodeling. However, the utilization of blank transfection reagent adversely affected wound closure in normal OECM-1 cells and reduced cell invasion in inflamed OECM-1 cells, thereby compromising the interpretation of miR-146a-5p in TNF-α-stimulated cellular behavior. Conclusions: Modulating miR-146a-5p can regulate the inflammatory response, and further investigation is needed to determine its impact on cell motility in OECM-1 cells, highlighting its potential role in linking periodontal inflammation to oral cancer progression.