Stepwise analysis of MIR9 loci identifies miR-9-5p to be involved in Oestrogen regulated pathways in breast cancer patients

Barbano, Raffaela; Pasculli, Barbara; Rendina, Michelina; Fontana, Andrea; Fusilli, Caterina; Copetti, Massimiliano; Castellana, Stefano; Valori, Vanna Maria; Morritti, Maria; Graziano, Paolo; Ciuffreda, Libero; Coco, Michelina; Picardo, Francesco; Mazza, Tommaso; Evron, Ella; Murgo, Roberto; Maiello, Evaristo; Esteller, Manel; Fazio, Vito Michele; Parrella, Paola

doi:10.1038/srep45283

Cited by 42 publications

(26 citation statements)

References 58 publications

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“…A subset of identified miRNAs was differentially regulated in ER− versus ER+ tumors, regardless of race. Top DEmiRs include miR-934, miR-9-3p/5p, miR-18a/18b, miR-135b and miR-190b, which showed expression changes consistent with results from our analysis of the TCGA dataset and from several previous studies (15,16,(23)(24)(25)(26). These observations are in line with the fact that most published studies have focused exclusively on EAs.…”

Section: Discussionsupporting

confidence: 91%

Differences in microRNA expression in breast cancer between women of African and European ancestry

Gong

Wang

et al. 2018

Carcinogenesis

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Breast cancer is a heterogeneous disease, characterized by molecularly and phenotypically distinct tumor subtypes, linked to disparate clinical outcomes. American women of African ancestry (AA) are more likely than those of European ancestry (EA) to be diagnosed with aggressive, estrogen receptor negative (ER−) or triple negative breast cancer, and to die of this disease. However, the underlying causes of AA predisposition to ER−/triple negative breast cancer are still largely unknown. In this study, we performed high-throughput whole-genome miRNA expression profiling in breast tissue samples from both AA and EA women. A number of differentially expressed miRNAs, i.e., DEmiRs defined as >2-fold change in expression and false discovery rate <0.05, were identified as up-or downregulated by tumor ER status or by ancestry. We found that among 102 ER-subtype-related DEmiRs identified in breast tumors, the majority of these DEmiRs were race specific, with only 23 DEmiRs shared in tumors from both AAs and EAs; this finding indicates that there are unique subsets of miRNAs differentially expressed between ER− and ER positive tumors within AAs versus EAs. Our overall results support the notion that miRNA expression patterns may differ not only by tumor subtype but by ancestry, indicating differences in tumor biology and heterogeneity of breast cancer between AAs and EAs. These results will provide the basis for further functional analysis to elucidate biological differences between AAs and EAs and to help develop targeted treatment strategies to reduce disparities in breast cancer.

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Section: Discussionsupporting

confidence: 91%

Differences in microRNA expression in breast cancer between women of African and European ancestry

Gong

Wang

et al. 2018

Carcinogenesis

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“…Few recent studies in gynaecological cancer research have described an association of miRNA and estrogen signalling. Most of them have described the role of miRNA to regulate ER expression and estrogen-associated molecules [15,16]. How E2 may interfere with the whole miRNA expression profile in the cardiovascular system is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez

Pérez‐Cremades

Mompeón

et al. 2018

Cell Physiol Biochem

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Background/Aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen. Methods: We used miRNA microarrays to determine global miRNA expression in human umbilical vein endothelial cells (HUVEC) exposed to a physiological concentration of estradiol (E2; 1 nmol/L) for 24 hours. miRNAgene interactions were computationally predicted using Ingenuity Pathway Analysis and changes in miRNA levels were validated by qRT-PCR. Role of ER in the E2-induced miRNA was additionally confirmed by using specific ER agonists and antagonists. Results: miRNA array revealed that expression of 114 miRNA were significantly modified after E2 exposition. Further biological pathway analysis revealed cell death and survival, lipid metabolism, reproductive system function, as the top functions regulated by E2. We validated changes in the most significantly increased (miR-30b-5p, miR-487a-5p, miR-4710, miR-501-3p) and decreased (miR-378h and miR-1244) miRNA and the role of ER in these E2-induced miRNA was determined. Results showed that both classical, ERα and ERβ, and membrane-bound ER, GPER, differentially regulated specific miRNA. In silico analysis of validated miRNA promoters identified specific ER binding sites. Conclusion: Our findings identify differentially expressed miRNA pathways linked to E2 in human endothelial cells through ER, and provide new insights by which estrogen can modulate endothelial function.

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“…Moreover, we found that serum exosomal miR-9-5p was up-regulated in early-stage GC. Likewise, up-regulation of miR-9-5p was observed in both breast cancer and lung cancer, which promoted tumor proliferation, invasion, and metastasis (Barbano et al, 2017). However, functional roles of miR-146b-5p and miR-9-5p in GC remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Combination of Four Serum Exosomal MiRNAs as Novel Diagnostic Biomarkers for Early-Stage Gastric Cancer

et al. 2020

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Gastric cancer (GC) remains a leading cause of cancer-related mortality in the United States and China, there is an urgent need to discover novel non-invasive biomarkers for the early diagnosis of GC to improve the prognosis of GC patients. Exosomal miRNAs are considered promising biomarkers for cancer diagnosis. Using next-generation sequencing (NGS), bioinformatics and further validation, we identified and evaluated exosomal miRNAs in serum as early diagnostic markers for GC. NGS revealed that the average mappable reads in the RNA libraries were about 6.5 million per patient including miRNAs (73.38%), rRNAs (17.10%), snRNAs (8.83%), snoRNAs (0.65%), and tRNAs (0.04%). A total of 66 up and 13 down-regulated exosomal miRNAs were found in the screened cohort. In the validation cohort, by comparing with healthy individuals, higher levels of serum exosomal miR-92b-3p, let-7g-5p, miR-146b-5p, and miR-9-5p were found to be significantly associated with early-stage GC (p < 0.05). Diagnostic power of the combined panels of the exosomal miRNAs or the combination of exosomal miRNAs and CEA outperformed that of single exosomal miRNA marker for establishing a diagnosis of early-stage GC. The combined diagnosis of exosomal miR-92b-3p + let-7g-5p + miR-146b-5p + miR-9-5p with CEA had the most powerful efficiency with an AUC up to 0.786. In addition, serum levels of exosomal miR-92b-3p were significantly associated with poor cohesiveness (p = 0.0021), let-7g-5p and miR-146b-5p were significantly correlated with nerve infiltration (p = 0.0234 and p = 0.0126, respectively), and miR146b-5p was statistically correlated with tumor invasion depth in early-stage GC (p = 0.0089). In conclusion, serum exosomal miR-92b-3p, -146b-5p, -9-5p, and let-7g-5p may serve as potential non-invasive biomarkers for early diagnosis of GC.

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Stepwise analysis of MIR9 loci identifies miR-9-5p to be involved in Oestrogen regulated pathways in breast cancer patients

Cited by 42 publications

References 58 publications

Differences in microRNA expression in breast cancer between women of African and European ancestry

Differences in microRNA expression in breast cancer between women of African and European ancestry

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Combination of Four Serum Exosomal MiRNAs as Novel Diagnostic Biomarkers for Early-Stage Gastric Cancer

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