Downregulation of microRNAs 145-3p and 145-5p Is a Long-term Predictor of Postmenopausal Breast Cancer Risk: The ORDET Prospective Study

Muti, Paola; Sacconi, Andrea; Hossain, Ahmed; Donzelli, Sara; Moshe, Noa Bossel Ben; Ganci, Federica; Sieri, Sabina; Berrino, Franco; Biagioni, Francesca; Strano, Sabrina; Beyene, Joseph; Yarden, Yosef; Blandino, Giovanni

doi:10.1158/1055-9965.epi-14-0398

Cited by 24 publications

(20 citation statements)

References 41 publications

(43 reference statements)

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“…The recent discovery of the circRNA–microRNA code, in which the two types of RNA molecules interact with one another to determine the regulation of gene expression, is a promising field of study for early detection and prognosis of cancer. Our previous studies described miRNAs that can serve as long‐term predictors of postmenopausal breast cancer risk, that is, miR‐145‐3p, miR‐145‐5p, and miR‐513a‐5p (Muti et al ., , ). To the best of our knowledge, there are no studies describing the role of circRNAs as long‐term predictors, but this role is likely to be uncovered.…”

Section: Known Mechanisms Of Action Of Circrnasmentioning

confidence: 99%

The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

Verduci¹,

Strano²,

et al. 2019

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Circular RNA s (circ RNA s) comprise an emerging new class of endogenous RNA s expressed abundantly by the eukaryotic transcriptome. They are characterized by a covalently closed loop structure, resulting in RNA molecules that are more stable than linear RNA s. A growing number of studies indicate that circ RNA s play critical roles in human diseases and show great potential as biomarkers and therapeutic targets. The molecular events determined by circ RNA activity, the circ RNA code, involve other types of noncoding RNA molecules, primarily micro RNA s, long noncoding RNA s, and RNA ‐binding proteins. Herein, we mainly focus on the circ RNA –micro RNA code, showing how this relationship impacts the regulation of gene expression in cancer. The emerging roles for circ RNA s in oncogenic pathways highlight new perspectives for the detailed molecular dissection of cancer pathogenesis and, at the same time, offer new opportunities to design innovative therapeutic strategies. Here, we review recent research advancements in understanding the biogenesis, molecular functions, and significance of circ RNA s in cancer diagnosis and treatment.

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Section: Known Mechanisms Of Action Of Circrnasmentioning

confidence: 99%

The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

Verduci¹,

Strano²,

et al. 2019

Self Cite

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“…Literature selection A total of 1,262 studies were identified from online databases MEDLINE, Embase, PubMed, Google Scholar, and China Biology Medicine disc. Another five studies (17,(38)(39)(40)(41) were acquired through manually screening the reference lists of relevant reviews and meta-analyses. After removing 54 duplicated publications, the remaining 1,213 studies were evaluated by carefully reading the titles and abstracts, after which 1,059 studies were excluded because of the following reasons: not tumor studies, unpublished, withdrawn articles, letters, abstracts, reviews, or meta-analyses.…”

Section: Resultsmentioning

confidence: 99%

“…In different studies, OS was also expressed as disease-specific survival (DSS; ref. 17) and cancer-specific survival (CSS; ref. 15), while PFS was also described as recurrence-free interval (RFI; ref.…”

Section: Outcomes and Definitionmentioning

confidence: 99%

The Prognostic Value and Regulatory Mechanisms of microRNA-145 in Various Tumors: A Systematic Review and Meta-analysis of 50 Studies

Zhang

Tang

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Acting as an important tumor-related miRNA, the clinical significance and underlying mechanisms of miR-145 in various malignant tumors have been investigated by numerous studies. This study aimed to comprehensively estimate the prognostic value and systematically illustrate the regulatory mechanisms of miR-145 based on all eligible literature.Relevant studies were acquired from multiple online databases. Overall survival (OS) and progression-free survival (PFS) were used as primary endpoints. Detailed subgroup analyses were performed to decrease the heterogeneity among studies and recognize the prognostic value of miR-145. All statistical analyses were performed with RevMan software version 5.3 and STATA software version 14.1. A total of 48 articles containing 50 studies were included in the meta-analysis. For OS, the pooled results showed that low miR-145 expression in tumor tissues was significantly associated with worse OS in patients with various tumors [HR ¼ 1.70; 95% confidence interval (CI), 1.46-1.99; P < 0.001). Subgroup analysis based on tumor type showed that the downregulation of miR-145 was associated with unfavorable OS in colorectal cancer (HR ¼ 2.17; 95% CI, 1.52-3.08; P < 0.001), ovarian cancer (HR ¼ 2.15; 95% CI, 1.29-3.59; P ¼ 0.003), gastric cancer (HR ¼ 1.78; 95% CI, 1.35-2.36; P < 0.001), glioma (HR ¼ 1.65; 95% CI, 1.30-2.10; P < 0.001), and osteosarcoma (HR ¼ 2.28; 95% CI, 1.50-3.47; P < 0.001). For PFS, the pooled results also showed that the downregulation of miR-145 was significantly associated with poor PFS in patients with multiple tumors (HR ¼ 1.39; 95% CI, 1.16-1.67; P < 0.001), and the subgroup analyses further identified that the low miR-145 expression was associated with worse PFS in patients with lung cancer (HR ¼ 1.97; 95% CI, 1.25-3.09; P ¼ 0.003) and those of Asian descent (HR ¼ 1.50; 95% CI, 1.23-1.82; P < 0.001). For the regulatory mechanisms, we observed that numerous tumor-related transcripts could be targeted by miR-145-5p or miR-145-3p, as well as the expression and function of miR-145-5p could be regulated by multiple molecules.This meta-analysis indicated that downregulated miR-145 in tumor tissues or peripheral blood predicted unfavorable prognostic outcomes for patients suffering from various malignant tumors. In addition, miR-145 was involved in multiple tumor-related pathways and the functioning of significant biological effects. miR-145 is a well-demonstrated tumor suppressor, and its expression level is significantly correlated with the prognosis of patients with multiple malignant tumors.

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“…The regulation of the mature 5p and 3p chains from several miRNAs has been investigated in other cancers, including colorectal, gastric, breast, lung, kidney, and bladder 36,72,[74][75][76][77] , suggesting the need to focus further studies on the two mature chains from the 272 miRNAs reported in this study. Figure 6 shows the complexity of the interactions between miRNAs and tumour suppressor genes, proto-oncogenes and oncogenes.…”

Section: Mirnas Located In Hpv Integration Sitesmentioning

confidence: 95%

Mapping of microRNAs related to cervical cancer in Latin American human genomic variants

et al. 2017

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MicroRNAs are related to human cancers, including cervical Background cancer (CC), which is mainly caused by human papillomavirus (HPV) infection. In 2012, approximately 70000 cases and 28000 deaths from this cancer were registered in Latin America according to GLOBOCAN reports. The most frequent genotype worldwide is HPV-16. The main molecular mechanism of HPV in CC is related to integration of viral DNA into the hosts' genome. However, the different variants in the human genome can result in different integration mechanisms, specifically involving microRNAs (miRNAs).: miRNA sequences associated with CC and four human genome Methods variants from Latin American populations were obtained from miRBase and the 1000 Genomes Browser, respectively. HPV integration sites near cell cycle regulatory genes were identified. miRNAs were mapped on human genomic variants. miRSNPs (single nucleotide polymorphisms in miRNAs) were identified in the miRNA sequences located at HPV integration sites on the human genomic Latin American variants.: Two hundred seventy-two miRNAs associated with CC were Results identified in 139 reports from different geographic locations. By mapping with the Blast-Like Alignment Tool (BLAT), 2028 binding sites were identified from these miRNAs on the human genome (version GRCh38/hg38); 42 miRNAs were located on unique integration sites; and miR-5095, miR-548c-5p and miR-548d-5p were involved with multiple genes related to the cell cycle. Thirty-seven miRNAs were mapped on the human Latin American genomic variants (PUR, MXL, CLM and PEL), but only miR-11-3p, miR-31-3p, miR-107, miR-133a-3p, miR-133a-5p, miR-133b, miR-215-5p, miR-491-3p, miR-548d-5p and miR-944 were conserved.: 10 miRNAs were conserved in the four human genome variants, Conclusions and in the remaining 27 miRNAs, substitutions, deletions or insertions were observed in the nucleotide sequences. This variability can imply differentiated mechanisms towards each genomic variant in human populations, relative to specific genomic patterns and geographic features. These findings may be decisive in determining susceptibility to the development of CC. Further identification of cellular genes and signalling pathways involved in CC progression could lead to the development of new therapeutic strategies based on miRNAs.

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Downregulation of microRNAs 145-3p and 145-5p Is a Long-term Predictor of Postmenopausal Breast Cancer Risk: The ORDET Prospective Study

Cited by 24 publications

References 41 publications

The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

The Prognostic Value and Regulatory Mechanisms of microRNA-145 in Various Tumors: A Systematic Review and Meta-analysis of 50 Studies

Mapping of microRNAs related to cervical cancer in Latin American human genomic variants

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