Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Oral Health
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Research

Network analysis reveals miRNA crosstalk between periodontitis and oral squamous cell carcinoma

Authors: Zhengrui Li, Rao Fu, Xutao Wen, Ling Zhang

Published in: BMC Oral Health | Issue 1/2023

Login to get access

Abstract

Background

Oral squamous cell carcinoma (OSCC) is one of the malignant tumors with a poor prognosis. Periodontitis (PD is considered a high-risk factor for OSCC, but the genetic mechanism is rarely studied. This study aims to link OSCC and PD by identifying common differentially expressed miRNAs (Co-DEmiRNAs), their related genes (Hub genes), transcription factors (TFs), signaling pathways, enrichment functions, and compounds, and searching for genetic commonalities.

Methods

The miRNAs expression datasets of OSCC and PD were searched from the GEO database. The miRNA and related crosstalk mechanism between OSCC and PD was obtained through a series of analyses.

Results

hsa-mir-497, hsa-mir-224, hsa-mir-210, hsa-mir-29c, hsa-mir-486-5p, and hsa-mir-31are the top miRNA nodes in Co-DEmiRNA-Target networks. The most significant candidate miRNA dysregulation genes are ZNF460, FBN1, CDK6, BTG2, and CBX6, while the most important dysregulation TF includes HIF1A, TP53, E2F1, MYCN, and JUN. 5-fluorouracil, Ginsenoside, Rh2, and Formaldehyde are the most correlated compounds. Enrichment analysis revealed cancer-related pathways and so on.

Conclusions

The comprehensive analysis reveals the interacting genetic and molecular mechanism between OSCC and PD, linking both and providing a foundation for future basic and clinical research.
Appendix
Available only for authorised users
Literature
1.
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries (vol 68, pg 394, 2018). Ca-a Cancer J Clinic. 2020;70(4):313–313.CrossRef
2.
Poveda-Roda R, Bagan JV, Jimenez-Soriano Y, Margaix-Munoz M, Sarrion-Perez G. Changes in smoking habit among patients with a history of oral squamous cell carcinoma (OSCC). Medicina Oral Patologia Oral Y Cirugia Bucal. 2010;15(5):E721–6.CrossRef
3.
Adeoye J, Tan JY, Ip CM, Choi SW, Thomson P. “Fact or fiction?”: Oral cavity cancer in nonsmoking, nonalcohol drinking patients as a distinct entity-scoping review. Head Neck-J Sci Special Head Neck. 2021;43(11):3662–80.CrossRef
4.
Rai AK, Freddy AJ, Chatterjee A. Raw betel-nut induced oral and esophageal cancers in Meghalaya. Oral Oncol. 2009;3:206.
5.
Laprise C, Shahul HP, Madathil SA, et al. Periodontal diseases and risk of oral cancer in Southern India: results from the HeNCe Life study. Int J Cancer. 2016;139(7):1512–9.CrossRef
6.
Shin KH, Park KH, Hong HJ, et al. Prevalence of microsatellite instability, inactivation of mismatch repair genes, p53 mutation, and human papillomavirus infection in Korean oral cancer patients. Int J Oncol. 2002;21(2):297–302.
7.
Ortiz AP, Gonzalez D, Ramos J, et al. Association of marijuana use with oral HPV infection and periodontitis among Hispanic adults: Implications for oral cancer prevention. J Periodontol. 2018;89(5):540–8.CrossRef
8.
Shin YJ, Choung HW, Lee JH, Rhyu IC, Kim HD. Association of periodontitis with oral cancer: a case-control study. J Dent Res. 2019;98(5):526–33.CrossRef
9.
Gonda K, Shibata M, Suzuki S, et al. Serum levels of vascular endothelial growth factor in patients with gastrointestinal cancers and correlation with malnutrition, immunosuppression involving MDSC, and systemic inflammation. J Clin Oncol. 2014;32(3):1682.
10.
Shibata M, Ujiie D, Ashizawa M, et al. Correlation of inflammation-related markers with MDSC and IL-17, and use as prognostic indicators in patients with advanced gastric and colorectal cancers. J Clin Oncol. 2019;37(15):e14204.CrossRef
11.
Gundogdu UD, Cenikh U, Coban FK, Tanriverdi O. Correlation of inflammation parameters with peripheral neuropathic pain in breast cancer patients underwent through paclitaxel chemotherapy. Fresenius Environ Bull. 2021;30(7a):9547–50.
12.
Contaldo M, Boccellino M, Zannini G, et al. Sex hormones and inflammation role in oral cancer progression: a molecular and biological point of view. J Oncol. 2020.
13.
Sfreddo CS, Maier J, De David SC, Susin C, Moreira CHC. Periodontitis and breast cancer: a case-control study. Commun Dent Oral Epidemiol. 2017;45(6):545–51.CrossRef
14.
Miskiewicz A, Szparecki G, Durlik M, et al. The Q705K and F359L single-nucleotide polymorphisms of NOD-like receptor signaling pathway: association with chronic pancreatitis, pancreatic cancer, and periodontitis. Arch Immunol Ther Exp. 2015;63(6):485–94.CrossRef
15.
Li X, Chaouhan HS, Li CH, et al. Higher risk of gastric helicobacter pylori infection in patients with periodontitis: a nationwide population-based retrospective cohort study in Taiwan. Int J Environ Res Public Health. 2021;18(21):11678.CrossRef
16.
Di Spirito F, Toti P, Pilone V, et al. The association between periodontitis and human colorectal cancer: genetic and pathogenic linkage. Life-Basel. 2020;10(9):211.CrossRef
17.
Komlos G, Csurgay K, Horvath F, Pelyhe L, Nemeth Z. Periodontitis as a risk for oral cancer: a case-control study. BMC Oral Health. 2021;21(1):640.CrossRef
18.
Javed F, Warnakulasuriya S. Is there a relationship between periodontal disease and oral cancer? A systematic review of currently available evidence. Crit Rev Oncol Hematol. 2016;97:197–205.CrossRef
19.
Wei L, Li SL, Zhang PC, et al. Characterizing microRNA-mediated modulation of gene expression noise and its effect on synthetic gene circuits. Cell Rep. 2021;36(8):109573.CrossRef
20.
Chen HW, Lai YC, Rahman MM, et al. Micro RNA differential expression profile in canine mammary gland tumor by next generation sequencing. Gene. 2022;818.
21.
Kanehisa M, Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 2000;28(1):27–30.CrossRef
22.
Amr KS, Atia HA, Elbnhawy RA, Ezzat WM. Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma. Genes Diseases. 2017;4(4):215–21.CrossRef
23.
Fan JQ, Xu GX, Chang ZB, Zhu L, Yao J. miR-210 transferred by lung cancer cell-derived exosomes may act as proangiogenic factor in cancer-associated fibroblasts by modulating JAK2/STAT3 pathway. Clin Sci. 2020;134(7):807–25.CrossRef
24.
Dickson MC, Ludbrook VJ, Perry HC, et al. A model of skin inflammation in humans leads to a rapid and reproducible increase in the interferon response signature: a potential translational model for drug development. Inflamm Res. 2015;64(3–4):171–83.CrossRef
25.
Li CH, Zhu ZY, Hou QS, et al. Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma. Transl Cancer Res. 2021;10(12):5319–36.CrossRef
26.
Wijaya RM, David A. microRNA identification on head and neck squamous cell carcinoma cancer gene based on male gender. Res J Biotechnol. 2021;16(8):50–4.CrossRef
27.
Denkceken T, Pala E. Investigation of key miRNAs and potential mechanisms in non-small cell lung cancer development from chronic obstructive pulmonary disease. Gen Physiol Biophys. 2020;39(1):69–77.CrossRef
28.
Tian LL, Qian B, Jiang XH, et al. MicroRNA-497-5p is downregulated in hepatocellular carcinoma and associated with tumorigenesis and poor prognosis in patients. Int J Genom. 2021.
29.
Jiang AM, Liu N, Bai SH, et al. The construction and analysis of tumor-infiltrating immune cells and ceRNA networks in bladder cancer. Front Genet. 2020;11.
30.
Zhang SW, Yue WX, Xie Y, et al. The four-microRNA signature identified by bioinformatics analysis predicts the prognosis of nasopharyngeal carcinoma patients. Oncol Rep. 2019;42(5):1767–80.
31.
Chen T, Zhu JJ, Cai TT, et al. Suppression of non-small cell lung cancer migration and invasion by hsa-miR-486-5p via the TGF-beta/SMAD2 signaling pathway. J Cancer. 2019;10(24):6014–24.CrossRef
32.
Monterde-Cruz L, Ramirez-Salazar EG, Rico-Martinez G, et al. MicroRNA expression in relation with clinical evolution of osteosarcoma. Pathol Res Pract. 2020;216(8):153038.CrossRef
33.
Staedel C, Darfeuille F. MicroRNAs and bacterial infection. Cell Microbiol. 2013;15(9):1496–507.CrossRef
34.
D. D. Niu, Y. E. Lii, P. Chellappan et al., "miRNA863–3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection," Nature Communications, vol. 7, 2016.
35.
K. L. Menard, B. E. Haskins, and E. Y. Denkers, "Impact of Toxoplasma gondii Infection on Host Non-coding RNA Responses," Frontiers in Cellular and Infection Microbiology, vol. 9, 2019.
36.
Y. S. Chen, J. Li, R. Menon et al., "Dietary spinach reshapes the gut microbiome in an Apc-mutant genetic background: mechanistic insights from integrated multi-omics," Gut Microbes, vol. 13, no. 1, 2021.
37.
Y. Liu, Z. R. Li, Y. X. Qi, X. T. Wen, and L. Zhang, "Metagenomic Analysis Reveals a Changing Microbiome Associated With the Depth of Invasion of Oral Squamous Cell Carcinoma," Frontiers in Microbiology, vol. 13, 2022.
38.
Y. X. Chen, Z. J. Huang, Z. M. Tang et al., "More Than Just a Periodontal Pathogen -the Research Progress on Fusobacterium nucleatum," Frontiers in Cellular and Infection Microbiology, vol. 12, 2022.
39.
Hao TF, Xu JN, Fang SF, et al. Overexpression of ZNF460 predicts worse survival and promotes metastasis through JAK2/STAT3 signaling pathway in patient with colon cancer. J Cancer. 2021;12(11):3198–208.CrossRef
40.
Zou C, Li X, Lv XZ, et al. Circular RNA mitochondrial translation optimization 1 homologue (CircMTO1) induced by zinc finger protein 460 (ZNF460) promotes oral squamous cell carcinoma progression through the microRNA miR-320a/alpha thalassemia/mental retardation, X-linked (ATRX) axis. Bioengineered. 2021;12(2):9585–97.CrossRef
41.
Pan MC, Li LJ, Li ZH, et al. Rare variants and polymorphisms of FBN1 gene May increase the risk of non-syndromic aortic dissection. Front Genet. 2022;13:778806.CrossRef
42.
Kono K, Maeda H, Fujii S, et al. Exposure to transforming growth factor-beta 1 after basic fibroblast growth factor promotes the fibroblastic differentiation of human periodontal ligament stem/progenitor cell lines. Cell Tissue Res. 2013;352(2):249–63.CrossRef
43.
Yang DY, Zhao DQ, Chen XR. MiR-133b inhibits proliferation and invasion of gastric cancer cells by up-regulating FBN1 expression. Cancer Biomark. 2017;19(4):425–36.CrossRef
44.
Botticelli A, Fabbri A, Roberto M, et al. The role of the CDK4/6 inhibitor ribociclib in locally advanced and oligometastatic hormone receptor positive, Her2 Negative, advanced breast cancer: case series and review of the literature. Front Oncol. 2022;12:797157.CrossRef
45.
Sharifi MN, Anandan A, Grogan P, O’Regan RM. Therapy after cyclin-dependent kinase inhibition in metastatic hormone receptor-positive breast cancer: resistance mechanisms and novel treatment strategies. Cancer. 2020;126(15):3400–16.CrossRef
46.
Petroni G, Formenti SC, Chen-Kiang S, Galluzzi L. Immunomodulation by anticancer cell cycle inhibitors. Nat Rev Immunol. 2020;20(11):669–79.CrossRef
47.
Wang X, Wang Y. LncRNA DCST1-AS1 inhibits PDLCs’ proliferation in periodontitis and may bind with miR-21 precursor to upregulate PLAP-1. J Periodontal Res. 2020;56(21):256.
48.
Mao BJ, Zhang ZM, Wang G. BTG2: A rising star of tumor suppressors. Int J Oncol. 2015;46(2):459–64.CrossRef
49.
Yuniati L, Scheijen B, van der Meer LT, van Leeuwen FN. Tumor suppressors BTG1 and BTG2: beyond growth control. J Cell Physiol. 2019;234(5):5379–89.CrossRef
50.
Yang X, Morita M, Wang H, et al. Crystal structures of human BTG2 and mouse TIS21 involved in suppression of CAF1 deadenylase activity. Nucleic Acids Res. 2008;36(21):6872–81.CrossRef
51.
Tsui KH, Lin YH, Chung LC, et al. Prostate-derived ets factor represses tumorigenesis and modulates epithelial-to-mesenchymal transition in bladder carcinoma cells. Cancer Lett. 2016;375(1):142–51.CrossRef
52.
Wang JM, He H, Jiang QC, Wang Y, Jia SZ. CBX6 promotes HCC metastasis via transcription factors Snail/Zeb1-mediated EMT mechanism. Onco Targets Ther. 2020;13:12489–500.CrossRef
53.
Chen DR, Wu LP, Liu L, et al. Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1 alpha and the osteogenic differentiation of PDLCs under hypoxia. Int J Mol Med. 2017;40(5):1529–36.CrossRef
54.
Kim YS, Shin SI, Kang KL, et al. Nicotine and lipopolysaccharide stimulate the production of MMPs and prostaglandin E-2 by hypoxia-inducible factor-1 alpha up-regulation in human periodontal ligament cells. J Periodontal Res. 2012;47(6):719–28.CrossRef
55.
Lin YF, Cheng TF, Zhu SY, et al. mRNA and long non-coding RNA expression profiling of human periodontal ligament cells under tension loading. Eur J Orthod. 2021;43(6):698–707.CrossRef
56.
Tiwari A, Tashiro K, Dixit A, et al. Loss of HIF1A from pancreatic cancer cells increases expression of PPP1R1B and degradation of p53 to promote invasion and metastasis. Gastroenterology. 2020;159(5):1882.CrossRef
57.
Rohwer N, Bindel F, Grimm C, et al. Annexin A1 sustains tumor metabolism and cellular proliferation upon stable loss of HIF1A. Oncotarget. 2016;7(6):6693–710.CrossRef
58.
Ambili R, Santhi WS, Janam P, Nandakumar K, Pillai MR. Expression of activated transcription factor nuclear Factor-kappa B in periodontally diseased tissues. J Periodontol. 2005;76(7):1148–53.CrossRef
59.
Nakazawa S, Sakata K, Liang S, et al. Dominant-negative p53 mutant R248Q increases the motile and invasive activities of oral squamous cell carcinoma cells. Biomed Res-Tokyo. 2019;40(1):37–49.CrossRef
60.
Sabit H, Tombuloglu H, Cevik E, et al. Knockdown of c-MYC controls the proliferation of oral squamous cell carcinoma cells in vitro via dynamic regulation of key apoptotic marker genes. Int J Mol Cell Med. 2021;10(1):45–55.
61.
Galea GL, Meakin LB, Harris MA, et al. Old age and the associated impairment of bones’ adaptation to loading are associated with transcriptomic changes in cellular metabolism, cell-matrix interactions and the cell cycle. Gene. 2017;599:36–52.CrossRef
62.
Shi WF, Hou XL, Li X, et al. Differential gene expressions of the MAPK signaling pathway in enterovirus 71-infected rhabdomyosarcoma cells. Braz J Infect Dis. 2013;17(4):410–7.CrossRef
63.
Dieterle MP, Husari A, Steinberg T, et al. Role of mechanotransduction in periodontal homeostasis and disease. J Dent Res. 2021;100(11):1210–9.CrossRef
64.
Zhao YC, Wang Y, Chen W, et al. Targeted intervention of eIF4A1 inhibits EMT and metastasis of pancreatic cancer cells via c-MYC/miR-9 signaling. Cancer Cell Int. 2021;21(1):670.CrossRef
65.
Ye F, Li JT, Xu PT, et al. Osteogenic differentiation of mesenchymal stem cells promotes c-Jun-dependent secretion of interleukin 8 and mediates the migration and differentiation of CD4(+) T cells. Stem Cell Res Therapy. 2022;13(1):58.CrossRef
66.
Sun Y, Zhao Y, Wang XP, et al. Wogonoside prevents colitis-associated colorectal carcinogenesis and colon cancer progression in inflammation-related microenvironment via inhibiting NF-kappa B activation through PI3K/Akt pathway. Oncotarget. 2016;7(23):34300–15.CrossRef
67.
Seshadri VD. Brucine promotes apoptosis in cervical cancer cells (ME-180) via suppression of inflammation and cell proliferation by regulating PI3K/AKT/mTOR signaling pathway. Environ Toxicol. 2021;36(9):1841–7.CrossRef
68.
Li S, Zhang Y, Gao AS, Zhang Y, Zhang J. Engelharquinone suppresses lipopolysaccharide-induced inflammation and proliferation of human liver cancer SMCC7721 cells via inhibition of NF-kappa B and MAPK signaling pathway. Trop J Pharm Res. 2020;19(4):699–706.CrossRef
69.
Vahed SZ, Barzegari A, Saadat YR, Goreyshi A, Omidi Y. Leuconostoc mesenteroides-derived anticancer pharmaceuticals hinder inflammation and cell survival in colon cancer cells by modulating NF-kappa B/AKT/PTEN/MAPK pathways. Biomed Pharmacother. 2017;94:1094–100.CrossRef
70.
Liu BW, Hu JC, Zhao H, Zhao L, Pan SY. MicroRNA-155-5p contributes to 5-fluorouracil resistance through down-regulating TP53INP1 in oral squamous cell carcinoma. Front Oncol. 2022;11:706095.CrossRef
71.
Novaes VCN, Ervolino E, Fernandes GL, et al. Influence of the treatment with the antineoplastic agents 5-fluorouracil and cisplatin on the severity of experimental periodontitis in rats. Support Care Cancer. 2022;30(3):1967–80.CrossRef
72.
Bi WY, Fu BD, Shen HQ, et al. Sulfated derivative of 20(S)-ginsenoside Rh2 inhibits inflammatory cytokines through MAPKs and NF-kappa B pathways in LPS-induced RAW264.7 macrophages. Inflammation. 2012;35(5):1659–68.CrossRef
73.
Wang YS, Chen C, Zhang SY, Li Y, Jin YH. (20S) Ginsenoside Rh2 inhibits STAT3/VEGF signaling by targeting annexin A2. Int J Mol Sci. 2021;22(17):9289.CrossRef
74.
Jiang S, Yan JQ, Chen XS, et al. Ginsenoside Rh2 inhibits thyroid cancer cell migration and proliferation via activation of miR-524-5p. Arch Med Sci. 2021;18(1):164–70.
75.
Li CC, Gao H, Feng XM, et al. Ginsenoside Rh2 impedes proliferation and migration and induces apoptosis by regulating NF-kappa B, MAPK, and PI3K/Akt/mTOR signaling pathways in osteosarcoma cells. J Biochem Mol Toxicol. 2020;34(12):e22597.CrossRef
76.
Bian S, Zhao Y, Li FY, et al. Knockdown of p62/sequestosome enhances ginsenoside Rh2-induced apoptosis in cervical cancer HeLa cells with no effect on autophagy. Biosci Biotechnol Biochem. 2021;85(5):1097–103.CrossRef
77.
Vishnu US, Esteve PO, Chin HG, Pradhan S. One-pot universal NicE-seq: all enzymatic downstream processing of 4% formaldehyde crosslinked cells for chromatin accessibility genomics. Epigenet Chrom. 2021;14(1):58.
78.
Protano C, Buomprisco G, Cammalleri V, et al. The carcinogenic effects of formaldehyde occupational exposure: a systematic review. Cancers. 2022;14(1):165.CrossRef
Metadata
Title
Network analysis reveals miRNA crosstalk between periodontitis and oral squamous cell carcinoma
Authors
Zhengrui Li
Rao Fu
Xutao Wen
Ling Zhang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-022-02704-2

Other articles of this Issue 1/2023

BMC Oral Health 1/2023 Go to the issue

Research

Is there any difference based on sublingual varices frequency between hypertensive patients and healthy persons?

Research

Systematic review fracture resistance of endodontically treated posterior teeth restored with fiber reinforced composites- a systematic review

Research

Clinical practice guideline adaptation for risk-based caries management in 18–55 year-old Iranian adults

Research

Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing

Research

Association between psychological stress, anxiety and oral health status among college students during the Omicron wave: a cross-sectional study

Research

Periodontists’ perceptions and attitudes toward the use of social media for professional purposes in Saudi Arabia