Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling

Zhang, Kai; Wang, Yawen; Wang, Yanyan; Song, Yu; Zhu, Jiang; Si, Pengchao; Ma, Rong

doi:10.1016/j.gene.2017.03.038

Cited by 84 publications

(75 citation statements)

References 42 publications

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“…To investigate the translational significance of these findings, we compared our list of circulating miRNA with the profiles of patients with breast cancer versus healthy controls in one of the very few publicly available datasets (GSE83270; ref. 34). Among the humanmouse homologous miRNAs (39/94), 11 were significantly upregulated in the blood of patients with breast cancer compared with healthy controls (Fig.…”

Section: Deregulated Mirnas Originate Mainly From Neoplastic Cells Anmentioning

confidence: 99%

Transcriptional Profiles and Stromal Changes Reveal Bone Marrow Adaptation to Early Breast Cancer in Association with Deregulated Circulating microRNAs

et al. 2020

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◥The presence of a growing tumor establishes a chronic state of inflammation that acts locally and systemically. Bone marrow responds to stress signals by expanding myeloid cells endowed with immunosuppressive functions, further fostering tumor growth and dissemination. How early in transformation the cross-talk with the bone marrow begins and becomes detectable in blood is unknown. Here, gene expression profiling of the bone marrow along disease progression in a spontaneous model of mammary carcinogenesis demonstrates that transcriptional modifications in the hematopoietic compartment occurred as early as preinvasive disease stages. The transcriptional profile showed downregulation of adaptive immunity and induction of programs related to innate immunity and response to danger signals triggered by activating transcription factor 3. Transcriptional reprogramming was paralleled by the expansion of myeloid populations at the expense of erythroid and B lymphoid fractions. Hematopoietic changes were associated with modifications of the bone marrow stromal architecture through relocalization and increased density in the interstitial area of Nestin þ mesenchymal cells expressing CXCL12 and myeloid cells expressing CXCL12 receptor CXCR4. These early events were concomitant with deregulation of circulating miRNAs, which were predicted regulators of transcripts downregulated in the bone marrow and involved in lymphoid differentiation and activation. These data provide a link between sensing of peripheral cancer initiation by the bone marrow and hematopoietic adaptation to distant noxia through transcriptional rewiring toward innate/ inflammatory response programs.Significance: The bone marrow senses distant tissue transformation at premalignant/preinvasive stages, suggesting that circulating messengers, intercepted in the blood, could serve as early diagnostic markers.

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Section: Deregulated Mirnas Originate Mainly From Neoplastic Cells Anmentioning

confidence: 99%

Transcriptional Profiles and Stromal Changes Reveal Bone Marrow Adaptation to Early Breast Cancer in Association with Deregulated Circulating microRNAs

et al. 2020

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“…Previous studies proposed that oncomiRs are frequently upregulated in BC and act via repressing the expression of tumor‐suppressor genes involved in cell cycle, apoptosis, cell proliferation and differentiation, migration, invasion, and metastasis (B. Zhang, Pan, Cobb, & Anderson, ). A very recent study identified 169 upregulated microRNAs (from 171 differently expressed microRNAs) in whole blood samples of the patients with BC (K. Zhang et al, ). The most prominent oncogenic microRNAs with upregulation in BC are listed in Table .…”

Section: Upregulated Oncomirs In Breast Cancermentioning

confidence: 99%

Key microRNAs in the biology of breast cancer; emerging evidence in the last decade

Khordadmehr

Shahbazi

Ezzati

et al. 2018

Journal Cellular Physiology

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microRNAs (miRNAs) are a family of small noncoding RNAs that play a pivotal role in the regulation of main biological and physiological processes, including cell cycle regulation, proliferation, differentiation, apoptosis, stem cell maintenance, and organ development. Dysregulation of these tiny molecules has been related to different human diseases, such as cancer. It has been estimated that more than 50% of these noncoding RNA sequences are placed on fragile sites or cancer‐associated genomic regions. After the discovery of the first specific miRNA signatures in breast cancer, many studies focused on the involvement of these small RNAs in the pathophysiology of breast tumors and their possible clinical implications as reliable prognostic biomarkers or as a new therapeutic approach. Therefore, the present review will focus on the recent findings on the involvement of miRNAs in the biology of breast cancer associated with their clinical implications.

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“…Comparing the distribution of these correlations of derived miR-96 targets against that of the background transcriptome revealed a significant shift toward negative correlations between miR-96 and its targets, supporting a functional relationship (p = 5.17e -7 ) ( Figure 7E). Interestingly, the motif for ONECUT2 was enriched in the experimentally derived RARg cistrome and has been previously identified as a miR-96 target 92 .…”

Section: Mir-96 Targets a Network Of Rarg Interacting Co-factorsmentioning

confidence: 85%

The miR-96 and RARγ signaling axis governs androgen signaling and prostate cancer progression

Long

Singh

Russell

et al. 2017

Preprint

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RARg (RARG) expression is commonly reduced in prostate cancer (PCa). Modulating RARg levels, not retinoid ligand, had the biggest impact on prostate cell proliferation and gene expression. Genomic binding of the non-liganded, apo, RARg was significantly enriched at active enhancers, associated with AR, and RARg knockdown governed the AR capacity to regulate cell differentiation and gene-regulation. Altered RARg target genes expression in TCGA significantly associated with more aggressive PCa. RARg downregulation was explained by a stark and common increase in miR-96 in PCa cell and animal models, and human PCa.Biochemical approaches confirmed that miR-96 directly regulates RARG expression and function. Capture of the miR-96 targetome by biotin-miRNA pulldown identified a RARg-centric network significantly associated with more aggressive PCa and worse disease free survival (hazard ratio 2.23, 95% CI 1.58 to 2.88, p=0.015). In summary, miR-96 targets an RARg network to govern AR signaling and its disruption is a cancer-driver. STATEMENT OF SIGNIFICANCE.We identified that miR-96 targets a RARg-network, which in turn regulates AR, PCa progression and disease outcome. These findings occur independently of retinoid ligand and reveal how miRNA govern nuclear receptor functions, and can be exploited to identify aggressive prostate cancer at an early stage.

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Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling

Cited by 84 publications

References 42 publications

Transcriptional Profiles and Stromal Changes Reveal Bone Marrow Adaptation to Early Breast Cancer in Association with Deregulated Circulating microRNAs

Transcriptional Profiles and Stromal Changes Reveal Bone Marrow Adaptation to Early Breast Cancer in Association with Deregulated Circulating microRNAs

Key microRNAs in the biology of breast cancer; emerging evidence in the last decade

The miR-96 and RARγ signaling axis governs androgen signaling and prostate cancer progression

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