Different miRNA expression profiles between human breast cancer turmors and serum
Ontology highlight
ABSTRACT: We identified total 174 significantly differentially expressed miRNAs between tumors and the normal tissues, and 109 miRNAs between serum from patients and serum from healthy individuals. There are only 10 common miRNAs. This suggests that only a small portion of tumor miRNAs are released into serum selectively. Interestingly, the expression change pattern of 28 miRNAs is opposite between breast cancer tumors and serum. Functional analysis shows that the differentially expressed miRNAs and their target genes form a complex interaction network affecting many biological processes and involving in cancer-related pathways such as prostate, basal cell carcinoma, acute myeloid leukymia, and more. A bunch of miRNAs have been demonstrated to be aberrantly expressed in cancer tumor tissue and serum. The miRNA signatures identified from the serum samples could serve as potential noninvasive diagnostic markers for breast cancer. The roles of the miRNAs in cancerigenesis is unclear. In this study, we generated the expression profiles of miRNAs from the paired breast cancer tumors, normal, tissue, and serum samples from eight patients using small RNA-sequencing. Serum samples from eight healthy individuals were used as normal controls.
Project description:We identified total 174 significantly differentially expressed miRNAs between tumors and the normal tissues, and 109 miRNAs between serum from patients and serum from healthy individuals. There are only 10 common miRNAs. This suggests that only a small portion of tumor miRNAs are released into serum selectively. Interestingly, the expression change pattern of 28 miRNAs is opposite between breast cancer tumors and serum. Functional analysis shows that the differentially expressed miRNAs and their target genes form a complex interaction network affecting many biological processes and involving in cancer-related pathways such as prostate, basal cell carcinoma, acute myeloid leukymia, and more.
Project description:To comprehensively characterize microRNA (miRNA) expression in breast cancer, we performed the first extensive next-generation sequencing expression analysis of this disease. We sequenced small RNA from tumors with paired samples of normal and tumor-adjacent breast tissue. Our results indicate that tumor identity is achieved mainly by variation in the expression levels of a common set of miRNAs rather than by tissue-specific expression. We also report 361 new, well-supported miRNA precursors. Nearly two-thirds of these new genes were detected in other human tissues and 49% of the miRNAs were found associated with Ago2 in MCF7 cells. Ten percent of the new miRNAs are located in regions with high-level genomic amplifications in breast cancer. A new miRNA is encoded within the ERBB2/Her2 gene and amplification of this gene leads to overexpression of the new miRNA, indicating that this potent oncogene and important clinical marker may have two different biological functions. In summary, our work substantially expands the number of known miRNAs and highlights the complexity of small RNA expression in breast cancer. Sequencing of approximately 18-35 nt small RNAs from paired samples of normal, tumor and tumor-adjacent tissue for five breast cancer patients
Project description:Numerous studies have described the altered expression and the causal role of miRNAs in human cancer. However, to date efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here, we find that Nucleolin (NCL), a major nucleolar protein, post-transcriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, causally involved in breast cancer initiation, progression and drug-resistance. We also show that NCL is commonly overexpressed in human breast tumors, and its expression correlates with that of NCL-dependent miRNAs. Finally, this study indicates that NCL-binding guanosine-rich aptamers affect the levels of NCL-dependent miRNAs and their target genes, reducing breast cancer cell aggressiveness, both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. Identification of NCL regulated miRNAs by using miRNA high-throughput sequencing of HeLa cells stably expressing double-strand (ds) interfering RNA against NCL or scrambled sequences (sh-NCL or sh-Scr).
Project description:MicroRNAs (miRNAs), which are stably present in serum, have been reported to be potentially useful for detecting cancer. In the present study, we examined the expression profiles of serum miRNAs in large cohorts to identify the miRNAs that can be used to detect breast cancer in the early stage. We comprehensively evaluated serum miRNA expression profiles using highly sensitive microarray analysis. A total of 1,280 serum samples of breast cancer patients stored in the National Cancer Center Biobank were used. Additionally, 2,836 serum samples were obtained from non-cancer controls and 514 from patients with other types of cancers or benign diseases. The samples were divided to a training cohort including non-cancer controls, other cancers and breast cancer and a test cohort including non-cancer controls and breast cancer. The training cohort was used to identify a combination of miRNAs that detect breast cancer, and the test cohort was used to validate that combination. miRNA expression was compared between breast cancer and non-breast cancer serum , and a combination of five miRNAs (miR-1246, miR-1307-3p, miR-4634, miR-6861-5p, and miR-6875-5p) was found to detect breast cancer. This combination had a sensitivity of 97.3%, specificity of 82.9%, and accuracy of 89.7% for breast cancer in the test cohort Additionally, the combination could detect breast cancer in the early stage (sensitivity of 98.0% for T0).
Project description:MicroRNAs (miRNAs), which are stably present in serum, have been reported to be potentially useful for detecting cancer. In the present study, we examined the expression profiles of serum miRNAs in large cohorts to identify the miRNAs that can be used to detect breast cancer in the early stage. We comprehensively evaluated serum miRNA expression profiles using highly sensitive microarray analysis. A total of 1,280 serum samples of breast cancer patients stored in the National Cancer Center Biobank were used. Additionally, 2,836 serum samples were obtained from non-cancer controls and 514 from patients with other types of cancers or benign diseases. The samples were divided to a training cohort including non-cancer controls, other cancers and breast cancer and a test cohort including non-cancer controls and breast cancer. The training cohort was used to identify a combination of miRNAs that detect breast cancer, and the test cohort was used to validate that combination. miRNA expression was compared between breast cancer and non-breast cancer serum , and a combination of five miRNAs (miR-1246, miR-1307-3p, miR-4634, miR-6861-5p, and miR-6875-5p) was found to detect breast cancer. This combination had a sensitivity of 97.3%, specificity of 82.9%, and accuracy of 89.7% for breast cancer in the test cohort Additionally, the combination could detect breast cancer in the early stage (sensitivity of 98.0% for T0). 1280 breast cancer serums (74 in training cohort, 1206 in test cohort), 54 benign breast diseases serums in test cohort, 2836 non-cancer control serums (1493 in training cohort, 1343 in test cohort), 514 non-breast benign diseases serums in training cohort. 150 of the non-cancer control serums in training cohort and 412 of the non-breast benign diseases serums in training cohort have been uploaded previously and are avaialable under GSE59856 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59856).
Project description:Tumor associated miRNAs in hereditary breast cancer. In this study we investigated the role of miRNAs in hereditary breast tumors comparing with normal breast tissue. Global miRNA expression profiling was performed on 22 hereditary breast tumors and 15 non-tumoral breast tissues. We identified 19 miRNAs differentially expressed, most of them down-regulated in tumors. An important proportion of deregulated miRNAs in hereditary tumors were previously identified commonly deregulated in sporadic breast tumors. Our results identify miRNAs associated to hereditary breast cancer, as well as miRNAs commonly miss-expressed in hereditary and sporadic tumors, suggesting common underlying mechanisms of tumor progression. In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling.
Project description:Tumor associated miRNAs in hereditary breast cancer. In this study we investigated the role of miRNAs in hereditary breast tumors comparing with normal breast tissue. Global miRNA expression profiling was performed on 22 hereditary breast tumors and 15 non-tumoral breast tissues. We identified 19 miRNAs differentially expressed, most of them down-regulated in tumors. An important proportion of deregulated miRNAs in hereditary tumors were previously identified commonly deregulated in sporadic breast tumors. Our results identify miRNAs associated to hereditary breast cancer, as well as miRNAs commonly miss-expressed in hereditary and sporadic tumors, suggesting common underlying mechanisms of tumor progression. In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling. Single color experiments in a pairwise comparison design.
Project description:Circulating microRNAs (c-miRNAs) have emerged as measurable biomarkers (liquid biopsies) for cancer detection. The goal of our study was to identify novel biomarkers to predict long-term breast cancer risk in cancer-free women. We evaluated the ability of c-miRNAs to identify women most likely to develop breast cancer by profiling miRNA from serum obtained long before diagnosis. 24 breast cancer cases and controls (matched for risk and age) were identified from women enrolled in the High-Risk Breast Program at the UVM Cancer Center. We used Affymetrix miRNA v4 microarrays to interrogate miRNAs (miRBase v20) in the serum of cancer-free women at high-risk for breast cancer. The 24 cases developed breast cancer at least 6 months (average of 3.2 years) and the 24 controls remain cancer-free.
Project description:microRNAs are small, non-coding, single-stranded RNAs between 18-22 nucleotides long that regulate gene expression. Expression of microRNAs is altered in tumor compared to normal tissue; there is some evidence that these changes may be reflected in the serum of cancer cases compared to healthy individuals. Several case-control studies have found evidence of differential levels of serum miRNAs in early stage non-small cell lung cancer (NSCLC) patients but with little consensus on specific miRNAs. Similarly, it is unclear whether miRNAs that show differential levels in tumors are the same miRNAs that are found in serum, and whether surgical resection of tumors leads to normalization of serum miRNA levels in cases. We used Affymetrix arrays to examine serum miRNA expression profiles in a small series of surgically resected non-small cell lung cancer cases to investigate circulating levels of miRNAs.
Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients. Two groups with n=7 per group; one groups represents cases with osteoporotic fractures, the control group is age-matched without fractures