{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:25:58Z","timestamp":1787696758542,"version":"build-2784847793"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Oral-gut pathogens are closely associated with pancreatic cancer, such as <jats:italic>Campylobacter jejuni, Clostridium difficile, Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Helicobacter pylori, Porphyromonas gingivalis<\/jats:italic>, and <jats:italic>Vibrio cholera<\/jats:italic>, but the related mechanisms remain not well understood. Phosphatase and tensin homolog (PTEN, a widely known tumor suppressor) play a key role in the anti-cancer immune system. Pancreatic cancer cells with PTEN loss are often in the immunosuppressive tumor microenvironment regulated by myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and M2 macrophages, which are regarded as the mechanism in the immune escape of cancers. The miR-21, as an oncogene in human cancers, plays an important role in pancreatic cancer progression, downregulates the levels of PTEN, and may promote cancer to evade host immune surveillance. Some oral-gut pathogens have been found to promote miR-21 expression and reduce PTEN expression. On the other hand, most gut pathogens infection is thought to produce reactive oxygen species (ROS) or activate inflammatory cytokines, which may also induce ROS-mediated miR-21 expression. These pathogens' infection is involved with the cell density of MDSCs, Tregs, and M2 macrophages. Therefore, it is quite reasonable to propose that oral-gut pathogens possibly promote pancreatic cancer escaping from host immune surveillance by activating the miR-21\/PTEN axis and immune-suppressive cells. The present exploration suggests that an increased understanding of the pattern of the effects of gut pathogens on the miR-21\/PTEN axis will lead to better insights into the specific mechanisms associated with the immune escape of pancreatic cancer caused by oral-gut microbiota.<\/jats:p>","DOI":"10.3389\/fmicb.2022.928846","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T16:37:25Z","timestamp":1655915845000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["An Exploration of Oral-Gut Pathogens Mediating Immune Escape of Pancreatic Cancer via miR-21\/PTEN Axis"],"prefix":"10.3389","volume":"13","author":[{"given":"Rui","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3606","DOI":"10.1158\/0008-5472.CAN-09-4598","article-title":"Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF","volume":"70","author":"Ali","year":"2010","journal-title":"Cancer Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/978-1-4939-7665-2_23","article-title":"Evaluation of macrophage polarization in pancreatic cancer microenvironment under hypoxia","volume":"2018","author":"Attri","year":"2018","journal-title":"Hypoxia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1338188","DOI":"10.1155\/2022\/1338188","article-title":"Clinical Analysis of Bloodstream Infection of Escherichia coli in Patients with Pancreatic Cancer from 2011 to 2019","volume":"2022","author":"Bai","year":"2022","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/S0732-8893(02)00412-1","article-title":"Splenic abscess with Vibrio cholerae masking pancreatic cancer","volume":"43","author":"Cavuoti","year":"2002","journal-title":"Diag. Microbiol. Infect. Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"21","DOI":"10.4142\/jvs.2020.21.e26","article-title":"In vivo multiplex gene targeting with Streptococcus pyogens and Campylobacter jejuni Cas9 for pancreatic cancer modeling in wild-type animal","author":"Chang","year":"2020","journal-title":"J. Vet. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3522","DOI":"10.3390\/cancers12123522","article-title":"Lactobacillus Attenuate the Progression of Pancreatic Cancer Promoted by Porphyromonas Gingivalis in K-rasG12D Transgenic Mice","volume":"12","author":"Chen","year":"2020","journal-title":"Cancers"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2018.02.010","article-title":"ADAM9 mediates the interleukin-6-induced Epithelial\u2013Mesenchymal transition and metastasis through ROS production in hepatoma cells","volume":"421","author":"Dong","year":"2018","journal-title":"Cancer Lett"},{"key":"B8","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/s12029-020-00433-9","article-title":"To study the anti-cancer effects of Shigella flexneri in AspC-1 pancreatic cancer cell line in approach to Bax and bcl-2 genes","volume":"52","author":"Khodavirdipour","year":"2021","journal-title":"J. Gastrointest. Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"835","DOI":"10.4251\/wjgo.v13.i8.835","article-title":"Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis","volume":"13","author":"Kunovsky","year":"2021","journal-title":"World J. Gastrointest. Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1200\/JCO.2014.57.4244","article-title":"Safety and survival with GVAX pancreas prime and Listeria monocytogenes\u2013expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer","volume":"33","author":"Le","year":"2015","journal-title":"J. Clin. Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.cell.2019.03.010","article-title":"A multiscale map of the stem cell state in pancreatic adenocarcinoma","volume":"177","author":"Lytle","year":"2019","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1016\/j.bbrc.2018.10.169","article-title":"Possible involvement of Enterococcus infection in the pathogenesis of chronic pancreatitis and cancer","volume":"506","author":"Maekawa","year":"2018","journal-title":"Biochem. Biophys. Res. Comm"},{"key":"B13","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s00262-014-1618-8","article-title":"Patients with pancreatic adenocarcinoma exhibit elevated levels of myeloid-derived suppressor cells upon progression of disease","volume":"64","author":"Markowitz","year":"2015","journal-title":"Cancer Immunol. Immunother"},{"key":"B14","doi-asserted-by":"publisher","first-page":"7209","DOI":"10.18632\/oncotarget.3109","article-title":"Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis","volume":"6","author":"Mitsuhashi","year":"2015","journal-title":"Oncotarget"},{"key":"B15","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.canlet.2009.06.033","article-title":"Rosmarinic acid sensitizes cell death through suppression of TNF-\u03b1-induced NF-\u03baB activation and ROS generation in human leukemia U937 cells","volume":"288","author":"Moon","year":"2010","journal-title":"Cancer Lett"},{"key":"B16","first-page":"1873","article-title":"Efficacy of a genetically-modified Salmonella typhimurium in an orthotopic human pancreatic cancer in nude mice","volume":"29","author":"Nagakura","year":"2009","journal-title":"Anticancer Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41577-021-00574-3","article-title":"CD8+ T cell differentiation and dysfunction in cancer","volume":"12","author":"Philip","year":"2021","journal-title":"Nat. Rev. Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/S2468-1253(19)30347-4","article-title":"The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"4","author":"Pourshams","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.biopha.2017.03.075","article-title":"Peroxiredoxin 4 inhibits IL-1\u03b2-induced chondrocyte apoptosis via PI3K\/AKT signaling","volume":"90","author":"Rao","year":"2017","journal-title":"Biomed. Pharmacother"},{"key":"B20","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.pan.2021.12.009","article-title":"Increased clostridium difficile infection in the era of preoperative chemotherapy for pancreatic cancer","volume":"22","author":"Sumiyoshi","year":"2022","journal-title":"Pancreatology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1038\/s41416-020-0834-6","article-title":"Emerging role of PTEN loss in evasion of the immune response to tumours","volume":"122","author":"Vidotto","year":"2020","journal-title":"Br. J. Cancer"},{"key":"B22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s11523-018-0616-8","article-title":"X, et al. Development of a novel EGFR-targeting antibody-drug conjugate for pancreatic cancer therapy","volume":"14","author":"Wang","year":"2019","journal-title":"Target. Oncol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1002\/cam4.626","article-title":"Micro RNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD 4","volume":"5","author":"Wei","year":"2016","journal-title":"Cancer Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1007\/s00432-020-03274-y","article-title":"The effects of NLRP3 inflammasome inhibition by MCC950 on LPS-induced pancreatic adenocarcinoma inflammation","volume":"146","author":"Yaw","year":"2020","journal-title":"J. Cancer Res. Clin. Oncol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12935-019-0728-y","article-title":"Long non-coding RNA CASC2 upregulates PTEN to suppress pancreatic carcinoma cell metastasis by downregulating miR-21","volume":"19","author":"Zhang","year":"2019","journal-title":"Cancer Cell Int"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.7150\/jca.37445","article-title":"Pancreatic cancer, gut microbiota, and therapeutic efficacy","volume":"11","author":"Zhang","year":"","journal-title":"J. Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"103822","DOI":"10.1016\/j.ebiom.2022.103822","article-title":"Attenuating DNA damage response and immunosuppression radiosensitizes pancreatic cancer","volume":"76","author":"Zhang","year":"2022","journal-title":"EBioMedicine"},{"key":"B28","doi-asserted-by":"publisher","first-page":"110160","DOI":"10.1016\/j.ecoenv.2019.110160","article-title":"ROS-mediated miR-21-5p regulates the proliferation and apoptosis of Cr (VI)-exposed L02 hepatocytes via targeting PDCD4","volume":"191","author":"Zhang","year":"","journal-title":"Ecotoxicol. Environ. Safety"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.928846\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T16:37:58Z","timestamp":1655915878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.928846\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,22]]},"references-count":28,"alternative-id":["10.3389\/fmicb.2022.928846"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.928846","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,22]]},"article-number":"928846"}}