Page 128 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

Serbian Association for Cancer Research SDIRSACR

Conclusions: Variations in ATG10 and ATG5 genes are associated with blood/inflammatory cells counts/ratios at BL and
clinical course of advanced melanoma.

Acknowledgments and funding: Science fund of Republic of Serbia, ReDiMEL project No 6795

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Identification and characterization of microRNAs involved in the progression from normal oral mucosa to
oral cancer

Katarina Zeljic1, Dunja Pavlovic2, Goran Stojkovic 3, 4

1University of Belgrade – Faculty of Biology, Belgrade, Serbia
2University of Belgrade – Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia
3University of Belgrade – Faculty of Medicine, Belgrade, Serbia
4University Clinical Center, Clinic for Otorhinolaryngology and Maxillofacial Surgery, Belgrade, Serbia

Keywords: oral mucosa, oral leukoplakia, oral cancer, miRNA

Background: The development of oral cancer is a complex, multistep process involving the transformation of normal
oral mucosa into premalignant lesions, such as oral leukoplakia with dysplasia, and eventually into oral cancer. A key
feature of this transformation is the deregulation of small non-coding RNA molecules, microRNAs (miRNAs). The
identification of miRNAs that are consistently deregulated at different stages of oral carcinogenesis is crucial to gaining
deeper insights into the molecular changes involved. Our aim was to identify and characterize commonly deregulated
miRNAs in normal oral mucosa, oral leukoplakia, and oral cancer using publicly available databases.
Material and Methods: The National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) was
utilized to identify databases containing miRNA expression data from normal oral mucosa, oral leukoplakia, and oral
cancer. Data from the GSE246050 dataset were analyzed using GEO2R software. Raw fastq files were retrieved from
Sequence Read Archive (SRP468035). HISAT2 and StringTie were used for identification and quantification of miRNA
transcripts. A list of miRNAs commonly deregulated was further characterised by miRNet v2.0 software.
Results: In total 112 genes were identified as commonly differentially deregulated across normal oral mucosa,
leukoplakia with dysplasia and oral cancer. Among them were 6 microRNA genes: MIR429, MIR6726, MIR135B,
MIR204, MIR139 and MIR211. Analysis of expression profiles of mature transcripts of these miRNA genes, revealed
significant changes in expression of hsa-miR-429, hsa-miR-135b-5p, hsa-miR-135b-3p, hsa-miR-204-5p, hsa-miR-139-
5p, hsa-miR-139-3p and hsa-miR-211-5p. We observed progressive upregulation of hsa-miR-429 and hsa-miR-135b-
5p/3p, while downregulation of hsa-miR-204-5p, hsa-miR-139-5p/3p and hsa-miR-211-5p in progression from normal
oral mucosa to oral cancer. To investigate the function of all genes regulated by miRNAs, a hypergeometric test and the
KEGG database were used. Pathways in cancer were significantly enriched with the largest number of genes.
Conclusions: Progression from normal oral mucosa to oral cancer might be characterized by up-regulation of hsa-
miR-429, hsa-miR-135b-5p/3p and down-regulation of hsa-miR-204-5p, hsa-miR-139-5p/3p and hsa-miR-211-5p.
These results are good starting point for further validation of miRNA candidates in oral carcinogenesis in a larger group
of clinical samples.

Acknowledgments and funding: This study was supported by the Ministry of Science, Technological Development and
Innovation of the Republic of Serbia [grant agreement: 451-03-137/2025-03/200178].

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