Mohammadi-Yeganeh, S. | bioRxiv Science

bioRxiv2025

Interplay of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans along with Circulating miR-21 and miR-155 as Potential Biomarkers for Pancreatic Cancer

The associations between oral bacterial pathogens and the risk of pancreatic cancer (PC) have been reported in several epidemiological studies. In this study, we evaluated the diagnostic potential of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in combination with circulating oncomiRNAs, including miR-21 and miR-155. A total of 41 PC patients and 40 age- and sex-matched controls were recruited for the study. The salivary bacterial load of P. gingivalis and A. actinomycetemcomitans, along with the copy number of miR-21 and miR-155 in blood, were measured using quantitative real-time PCR. Subsequently, the predictive power of the selected biomarkers in PC diagnosis was determined. Elevated load of the periodontal pathogens P. gingivalis in females (OR=2.31; 95% CI 0.98-5.47) and A. actinomycetemcomitans in diabetic individuals (OR=3.66; 95% CI 0.47-6.68) were associated with a higher risk of PC. Moreover, the diagnostic model incorporating two salivary species and two circulating miRNAs demonstrated an AUC of 0.878 (95% CI 0.802-0.955). This study offers compelling new evidence supporting the idea that the combined analysis of salivary microbiota and circulating miRNAs serves as an informative avenue for the discovery of non-invasive biomarkers for PC.

molecular biology↗

bioRxiv2018

miR-216b-5p is Down-Regulated in Human Breast Cancer and Inhibits Proliferation and Progression by Targeting HDAC8 Oncogene

BackgroundPrevious studies showed the role of histone deacetylases (HDACs) on the progression of some malignancies. Recently, there is more attention to therapeutic applications of epigenetic factors such as microRNAs (miRs). To the best of our knowledge, there are no other results regarding the contribution of miR-216b-5p and its potential target, HDAC8, in progression of cancer.\n\nAimIn the present study, we investigated the role of miR-216b-5p on HDAC8 and there following impacts on breast cancer (BC) progression.\n\nMethodsHuman BC specimens and noncancerous tissues were acquired from Iran Tumor Bank (I.T.B). The MDA-MB-231, MCF-7 and MCF-10A BC cell lines were also prepared. The tissue and cell line expression levels of miR-216b-5p and HDAC8 were determined by quantitative real-time PCR (qPCR). Protein levels of HDAC8 were also measured by Western blotting assay. The cell cycle, cell proliferation and colony formation assay were determined and the role of HDAC8 was investigated using a knockout vector. Targeting the 3' untranslated region (3'UTR) of HDAC8 by miR-216b-5p were confirmed using a luciferase reporter assay.\n\nResultsOur results show the significant decline in miR-216b-5p and highly increase in HDAC8 levels in human breast cancer tissues and cell lines. Overexpression of miR-216b-5p in BC cell lines inhibited cellular proliferation and progression and inhibition of miR-216b-5p reverse these effects. We also confirmed that HDAC8 is directly down-regulated by miR-216b-5p. Knockout of HDAC8 had also the effects as miR-216b-5p overexpression. Furthermore, we found that lower levels of miR-216b-5p are negatively correlated with lymph node metastasis and advanced tumor size.\n\nConclusionTaken together, our data shown that targeted overexpression of miR-216b-5p can suppress the growth of BC cells down-regulation of HDAC8. Therefore, inhibition of HDAC8 by miR-216b-5p will be helpful developing newer therapies for the effective treatment of BC.

cancer biology↗