Tumor surveillance by circulating microRNAs: a hypothesis.
Ontology highlight
ABSTRACT:
SUBMITTER: Igaz I
PROVIDER: S-EPMC4194016 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We previously detected and investigated nine altered microRNAs in small intestinal neuroendocrine tumor (SI-NET) tissues at different stages of disease. The aims of this study are to: 1) analyze whether SI-NET tissue microRNAs can be also detected in patient serum samples, 2) investigate a potential somatostatin analogs (SSAs) role on microRNA levels regulation in SSA-treated patient samples and 3) elucidate whether the serum microRNA levels in samples collected in different hospitals are predictable and steady. Our results show that tissue microRNAs are detectable in patient serum samples, and miR-96, -182, -183, -196a and -200a levels are lower in SI-NET untreated patients than in SSA-treated patients at all different stages. Conversely, miR-31, -129-5p, -133a and -215 levels do not show any difference in untreated SI-NET patients and SSA-treated patients at all different stages. Our findings also show that miR-200a exhibits an atypical behavior with high levels in both untreated and SSA-treated patients at liver metastasis stage, and unequivocally never at the earlier stages. Serum samples collected in two hospitals keep alike microRNA level pattern, elucidating that the results are not dependent on samples handling. In conclusion, SI-NET tissue microRNAs are always detectable in untreated and SSA-treated patient serum samples, SSAs play an unknown role in eliciting SSA-treated patients' microRNA levels higher than in untreated patients, and this study enlightens that miR-200a might be involved in the liver metastasis during SI-NET progression.
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Project description:MicroRNAs (miRNAs) are stable, small non-coding RNAs that modulate many downstream target genes. Recently, circulating miRNAs have been detected in various body fluids and within exosomes, prompting their evaluation as candidate biomarkers of diseases, especially cancer. Kaposi's sarcoma (KS) is the most common AIDS-associated cancer and remains prevalent despite Highly Active Anti-Retroviral Therapy (HAART). KS is caused by KS-associated herpesvirus (KSHV), a gamma herpesvirus also associated with Primary Effusion Lymphoma (PEL). We sought to determine the host and viral circulating miRNAs in plasma, pleural fluid or serum from patients with the KSHV-associated malignancies KS and PEL and from two mouse models of KS. Both KSHV-encoded miRNAs and host miRNAs, including members of the miR-17-92 cluster, were detectable within patient exosomes and circulating miRNA profiles from KSHV mouse models. Further characterization revealed a subset of miRNAs that seemed to be preferentially incorporated into exosomes. Gene ontology analysis of signature exosomal miRNA targets revealed several signaling pathways that are known to be important in KSHV pathogenesis. Functional analysis of endothelial cells exposed to patient-derived exosomes demonstrated enhanced cell migration and IL-6 secretion. This suggests that exosomes derived from KSHV-associated malignancies are functional and contain a distinct subset of miRNAs. These could represent candidate biomarkers of disease and may contribute to the paracrine phenotypes that are a characteristic of KS.
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Project description:Understanding the interaction between cancer cells and immunocytes will inspire new cancer therapy strategies. However, how cancer-derived circulating miRNAs modulate such interaction remains unclear. Here we discovered that circulating miR-410-5p, secreted by prostate cancer cells, entered dendritic cells (DCs), with the aid of argonaute-2 protein. The cancer cell antigens stimulated the DCs to produce miR-410-3p, a highly complementary counterpart of miR-410-5p derived from pre-miR-410. The DC-internalized miR-410-5p degraded the miR-410-3p by base pairing and thus inhibited its function in suppressing tumor angiogenesis, promoting tumor growth. Furthermore, blockade of the miR-410-5p upregulated the miR-410-3p to inhibit tumor growth. Our work suggests a new miRNA-mediated role of immunocytes in cancer progression and a new strategy of cancer therapy through suppressing circulating miRNAs.
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Project description:MicroRNAs are small noncoding RNAs that play an important role in the regulation of various biological processes through their interaction with cellular messenger RNAs. They are frequently dysregulated in cancer and have shown great potential as tissue-based markers for cancer classification and prognostication. microRNAs are also present in extracellular human body fluids such as serum, plasma, saliva, and urine. Most of circulating microRNAs are present in human plasma and serum cofractionate with the Argonaute2 (Ago2) protein. However, circulating microRNAs have been also found in membrane-bound vesicles such as exosomes. Since microRNAs circulate in the bloodstream in a highly stable, extracellular form, they may be used as blood-based biomarkers for cancer and other diseases. A knowledge base of extracellular circulating miRNAs is a fundamental tool for biomedical research. In this work, we present miRandola, a comprehensive manually curated classification of extracellular circulating miRNAs. miRandola is connected to miRò, the miRNA knowledge base, allowing users to infer the potential biological functions of circulating miRNAs and their connections with phenotypes. The miRandola database contains 2132 entries, with 581 unique mature miRNAs and 21 types of samples. miRNAs are classified into four categories, based on their extracellular form: miRNA-Ago2 (173 entries), miRNA-exosome (856 entries), miRNA-HDL (20 entries) and miRNA-circulating (1083 entries). miRandola is available online at: http://atlas.dmi.unict.it/mirandola/index.html.
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Project description:ImportanceFor patients with resected, nonmetastatic colorectal cancer (CRC), the optimal surveillance protocol remains unclear.ObjectiveTo evaluate whether serial circulating tumor DNA (ctDNA) levels detected disease recurrence earlier, compared with conventional postoperative surveillance, in patients with resected CRC.Design, setting, and participantsThis study included patients (n = 58) with stage I, II, or III CRC who underwent radical surgical resection at 4 Swedish hospitals from February 2, 2007, to May 8, 2013. Eighteen patients received adjuvant chemotherapy at the discretion of their clinicians, who were blinded to the ctDNA results. Blood samples were collected at 1 month after the surgical procedure and every 3 to 6 months thereafter for ctDNA analysis. Patients were followed up until metachronous metastases were detected, or for a median of 49 months. Data analysis was performed from March 1, 2009, to June 23, 2018.Main outcomes and measuresSensitivity and timing of ctDNA positivity were compared with those of conventional surveillance modalities (computed tomographic scans and serum carcinoembryonic antigen tests) for the detection of disease recurrence.ResultsThis study included 319 blood samples from 58 patients, with a median (range) age of 69 (47-83) years and 34 males (59%). The recurrence rate among patients with positive ctDNA levels was 77% (10 of 13 patients). Positive ctDNA preceded radiologic and clinical evidence of recurrence by a median of 3 months. Of the 45 patients with negative ctDNA throughout follow-up, none (0%; 95% CI, 0%-7.9%) experienced a relapse, with a median follow-up of 49 months. However, 3 (6%; 95% CI, 1.3%-17%) of the 48 patients without relapse had a positive ctDNA result, which subsequently fell to undetectable levels during follow-up.Conclusion and relevanceAlthough these findings need to be validated in a larger, prospective trial, they suggest that ctDNA analysis could complement conventional surveillance strategies as a triage test to stratify patients with resected CRC on the basis of risk of disease recurrence.
| S-EPMC6512291 | biostudies-literature
Project description:Gastrointestinal cancer (GIC) is a common disease and is considered to be the leading cause of cancer-related death worldwide; thus, new diagnostic and therapeutic strategies for GIC are urgently required. Noncoding RNAs (ncRNAs) are functional RNAs that are transcribed from the genome but do not encode proteins. MicroRNAs (miRNAs) are short ncRNAs that are reported to function as both oncogenes and tumor suppressors. Moreover, several miRNA-based drugs are currently proceeding to clinical trials for various diseases, including cancer. In recent years, the stability of circulating miRNAs in blood has been demonstrated. This is of interest because these miRNAs could be potential noninvasive biomarkers of cancer. In this review, we focus on circulating miRNAs associated with GIC and discuss their potential as novel biomarkers.
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Project description:MicroRNAs have been identified as key regulators of gene expression and thus their potential in disease diagnostics, prognosis and therapy is being actively pursued. Deregulation of microRNAs in cerebral pathogenesis has been reported to a limited extent in both animal models and human. Due to the complexity of the pathology, identifying stroke specific microRNAs has been a challenge. This study shows that microRNA profiles reflect not only the temporal progression of stroke but also the specific etiologies. A panel of 32 microRNAs, which could differentiate stroke etiologies during acute phase was identified and verified using a customized TaqMan Low Density Array (TLDA). Furthermore we also found 5 microRNAs, miR-125b-2*, -27a*, -422a, -488 and -627 to be consistently altered in acute stroke irrespective of age or severity or confounding metabolic complications. Differential expression of these 5 microRNAs was also observed in rat stroke models. Hence, their specificity to the stroke pathology emphasizes the possibility of developing these microRNAs into accurate and useful tools for diagnosis of stroke.
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Project description:BackgroundCirculating tumor cells (CTCs) are metastatic cells disseminated into the bloodstreams. They have been proposed to monitor disease progression for decades. However, the prognostic value of CTCs in gastric cancer (GC) remains controversial. We performed a meta-analysis to investigate the topic.MethodsA systematic search was made for relevant studies in academic data bases, involving the Medline, Embase, and Science Citation Index. Data on prognosis of GC patients, such as recurrence-free survival (RFS) and overall survival (OS), were extracted when possible. The meta-analysis was performed with the random effects model and the pooled hazard ratios (HRs) and their associated 95% confident intervals (95%CIs) were computed as effect measures.ResultsTwenty six studies (including 40 subgroups) with peripheral blood samples of 1950 cases from 10 countries were included in the final analysis. The pooled results showed that GC patients with detectable CTCs (including circulating miRNAs) had a tendency to experience shortened RFS (HR=2.91, 95% CI [1.84-4.61], I2=52.18%, n=10). As for patient deaths, we found a similar association of CTC (including circulating miRNAs) presence with worse OS (HR=1.78, 95% CI [1.49-2.12], I2=30.71%, n=30). Additionally, subgroup analyses indicated strong prognostic powers of CTCs, irrespective of geographical, methodological, detection time and sample size differences of the studies.ConclusionsOur meta-analysis shows that CTCs (including circulating miRNAs) can predict the survival of GC patients. Large prospective studies are warranted to determine the best sampling time points, detection methods in homogeneous patients with GC in the future.
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Project description:Circulating microRNAs (miRNAs) are considered as reliable candidates for biomarker discovery. RNA-Sequencing has become the most suitable technique to accurately quantify the miRNAome. However, RNA-Sequencing relies on several technical passages before reaching the final-end. HTG EdgeSeq technology, thanks to the abrogation of RNA extraction step, allows productivity enhancement by reducing the number of hands-on steps, the time for sample preparation and, therefore, the costs. We found a strong correlation between qPCR and dPCR with HTG (Pearson's coefficient of 0.93 and 0.94, respectively). In conclusion, we showed that HTG EdgeSeq, performed on human plasma specimens without RNA extraction, is reliable, allows the simultaneous screening of more than 2,000 miRNAs, and thus, it could be applied to biomarker discovery in large cohorts.
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