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치주세균에 감염된 구강암 세포 Ca9-22에서 유래한 exosomal small RNA 특성 및 기능 분석 Analysis on Exosomal Small RNA Derived from Periodontal Pathogen-infected Ca9-22 Oral Cancer Cells

유연이, 유미라, 김다정, 김윤학, 박혜련
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대한구강악안면병리학회지
제46권 제5호 (2022.10)
pp.83-90
대한구강악안면병리학회 (Korean Academy Of Oral And Maxillofacial Pathology)
초록

Porphyromonas gingivalis, a major pathogen of chronic periodontitis, colonizes in subgingival crevice and affects surrounding oral tissues, especially in periodontitis patients. Oral cancer mainly occurs in old-aged persons, and are exposed to the P. gingivalis, released from periodontitis, one of the most common inflammatory disease of oral cavity. Thus oral cancer cells may be infected with P. gingivalis, and its biologic behavior are autologously and/or heterogeneously modulated by altering gene expression. Exosomes which are derived from cells contain not only coding genes but also non-coding RNAs such as long non-coding RNAs, miRNA, and piRNAs. Here, to investigate the effect of P. gingivalis on oral cancer cells and to gain insight into the crosstalk between inflammatory signal from tumor microenvironment and oral cancer, we observed miRNA profiles of exosomes from P. gingivalis–infected oral cancer cells. Upregulation of 6 miRNAs, miR-203-3p, miR-6516-3p, miR-483-5p, miR-1275, miR-8485, and miR-19a-3p, were observed whereas 14 miRNAs including let-7a-3p, miR-106a-5p were downregulated. In addition, KEGG pathway analysis using the upregulated- and downregulated- miRNAs showed association with cell adhesion molecules pathway and ECM-receptor interaction pathway, respectively. These findings suggest that P. gingivalis could modulate biologic behavior of oral cancer cells through changes of exosomal miRNAs.

키워드
Periodontal pathogenOral cancerPeriodontitismiRNAExosomal Small RNA
목차
Abstract
Ⅰ. INTRODUCTION
Ⅱ. MATERIALS and METHODS
    1. 구강암세포 배양
    2. 치주세균 P. gingivalis 배양 및 P. gingivalis감염
    3. 엑소좀 분리
    4. miRNA 분리 및 분석
    5. 통계 분석
    6. Kyoto Encyclopedia of Genes and Genomes(KEGG) 경로 분석
Ⅲ. RESULTS
    1. P. gingivalis에 감염된 구강암세포 배양상층액에 포함된 엑소좀 유래 RNA-sequencing
    2. Heatmap 분석 기반 엑소좀 유래 miRNA프로파일링
    3. 치주세균에 의해 변화된 miRNA 연관 KEGG경로 분석
Ⅳ. DISCUSSION
ACKNOWLEDGMENTS
REFERENCES
저자
  • 유연이(부산대학교 의과대학 의학연구원) | Yeuni Yu (Biomedical Research Institute, School of Medicine, Pusan National University)
  • 유미라(부산대학교 치의학전문대학원 구강병리학교실) | Mi Ra Yu (Department of Oral Pathology, School of Dentistry, Pusan National University)
  • 김다정(부산대학교 치의학전문대학원 구강병리학교실) | Da Jeong Kim (Department of Oral Pathology, School of Dentistry, Pusan National University)
  • 김윤학(부산대학교 의과대학 해부학교실) | Yun Hak Kim (Department of Anatomy, School of Medicine, Pusan National University)
  • 박혜련(부산대학교 치의학전문대학원 구강병리학교실,부산대학교 치의학전문대학원 BK21플러스 사업단) | Hae Ryoun Park (Department of Oral Pathology, School of Dentistry, Pusan National University,BK21 PLUS Project, School of Dentistry, Pusan National University) Corresponding author