Dataset Information

Exosomal MicroRNAs in Pregnancy Provides Insight into a Possible Cure for Cancer.

ABSTRACT: The biological links between cancer and pregnancy are of recent interest due to parallel proliferative, immunosuppressive and invasive mechanisms between tumour and trophoblast development. Therefore, understanding "cancer-like" mechanisms in pregnancy could lead to the development of novel cancer therapeutics, however, little is understood on how tumour and trophoblast cells recapitulate similar molecular mechanisms. Based on our observations from a previous study, it was not only evident that exosomal miRNAs are involved in the pathophysiology of preeclampsia but also contained cancer-specific miRNAs, which suggested that "pseudo-malignant-like" exosomal-mediated mechanisms exist in pregnancy. The presented study therefore aimed to identify exosomal miRNAs (exomiR) in pregnancy which can be repurposed towards preventing tumour metastasis and immunosuppression. It was identified that exomiR-302d-3p, exomiR-223-3p and exomiR-451a, commonly associated with cancer metastasis, were found to be highly expressed in pregnancy. Furthermore, computational merging and meta-analytical pathway analysis (DIANA miRPath) of significantly expressed exomiRs between 38 ± 1.9 vs. 30 ± 1.11 weeks of gestation indicated controlled regulation of biological pathways associated with cancer metastasis and immunosuppression. Therefore, the observations made in this study provide the experimental framework for the repurposing of exosomal miRNA molecular mechanisms in pregnancy towards treating and preventing cancer.

SUBMITTER: Pillay P

PROVIDER: S-EPMC7432616 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exosomal MicroRNAs in Pregnancy Provides Insight into a Possible Cure for Cancer.

Pillay Preenan P Moodley Kogi K Vatish Manu M Moodley Jagidesa J

International journal of molecular sciences 20200729 15

The biological links between cancer and pregnancy are of recent interest due to parallel proliferative, immunosuppressive and invasive mechanisms between tumour and trophoblast development. Therefore, understanding "cancer-like" mechanisms in pregnancy could lead to the development of novel cancer therapeutics, however, little is understood on how tumour and trophoblast cells recapitulate similar molecular mechanisms. Based on our observations from a previous study, it was not only evident that ...[more]

PMID: 32751127

Similar Datasets

Project description:PURPOSE: Exosomal microRNAs (miRNAs) have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC). To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined. EXPERIMENTAL DESIGN: Microarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA) using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients. RESULTS: The serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a) were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis. CONCLUSION: Exosomal miRNA signatures appear to mirror pathological changes of CRC patients and several miRNAs are promising biomarkers for non-invasive diagnosis of the disease.

Project description:MicroRNAs (miRNAs) serve important roles in drug‑resistance; however, exosomal miRNAs associated with drug‑resistance in ovarian cancer (OC) have not been reported to date. The current study aimed to analyze the drug resistance‑associated exosomal miRNAs in original OC cells and their derived exosomes using microarray data downloaded from the Gene Expression Omnibus database (series GSE76449). The chemosensitive OC cell lines SKOV3_ip1, A2780_PAR and HEYA8, as well as the chemoresistant cell lines SKOV3_TR, A2780_CP20 and HEYA8_MDR, were investigated. Differentially expressed miRNAs (DE‑miRNAs) were identified using the limma method, and their mRNA targets were predicted using the miRWalk and LinkedOmics database. Functions of target genes were analyzed with DAVID tool, while TCGA data were used to explore the survival association of identified miRNAs. According to the results, 28 DE‑miRNAs were found to be common in exosomal and original samples of A2780_CP20 cells, among which the functions of 5 miRNAs were predicted (including miR‑146b‑5p, miR‑509‑5p, miR‑574‑3p, miR‑574‑5p and miR‑760). In addition, 16 and 35 DE‑miRNAs were detected for HEYA8_MDR and SKOV3_TR, respectively, with the functions of 4 of these miRNAs predicted for each cell line (HEYA8_MDR: miR‑30a‑3p, miR‑30a‑5p, miR‑612 and miR‑617; SKOV3_TR: miR‑193a‑5p, miR‑423‑3p, miR‑769‑5p and miR‑922). It was also reported that miR‑183‑5p was the only one common miRNA among the three cell lines. Furthermore, miR‑574‑3p, miR‑30a‑5p and miR‑922 may regulate CUL2 to mediate HIF‑1 cancer signaling pathway, while miR‑183‑5p may modulate MECP2, similar to miR‑760, miR‑30a‑5p and miR‑922, to influence cell proliferation. Finally, the downregulated miR‑612 may promote the expression of TEAD3 via the Hippo signaling pathway, and this miRNA was associated with poor prognosis. In conclusion, the findings of the present study suggested several underlying miRNA targets for improving the chemotherapy sensitivity of OC.

Dataset Information

Exosomal MicroRNAs in Pregnancy Provides Insight into a Possible Cure for Cancer.

Publications

Exosomal MicroRNAs in Pregnancy Provides Insight into a Possible Cure for Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure