Previously undescribed thyroid-specific miRNA sequences in papillary thyroid carcinoma

Barros-Filho, Mateus Camargo; Pewarchuk, Michelle E.; Minatel, Brenda C.; Sage, Adam P.; Marshall, Erin A.; Martínez, Victor D.; Rock, Leigha D.; MacAulay, Gavin; Kowalski, Luiz Paulo; Rogatto, Sílvia Regina; Garnis, Cathie; Lam, Wan L.

doi:10.1038/s10038-019-0583-7

Cited by 8 publications

(7 citation statements)

References 20 publications

(19 reference statements)

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“…Therefore, cell lineage- and tissue-specific miRNAs, especially those that are less abundant, may not be included in current miRBase annotations (29). This study, like several recent studies of other organs, has shown that re-analyses of high-throughput sequencing data, can lead to large-scale discoveries of novel miRNAs that are expressed in a tissue-specific manner, thus expanding the human miRNA transcriptome (29–33).…”

Section: Discussionsupporting

confidence: 58%

“…While current miRNA repositories contain ~2,500 unique miRNA sequences, they are primarily comprised of those that are either conserved across several tissues or abundantly expressed, for the most part discounting lineage- and tissue-specific miRNAs (28). However, recent studies show that numerous miRNAs may be expressed only in specific tissues or contexts (29–33), and may have utility as clinical markers of disease (8, 34).…”

Section: Introductionmentioning

confidence: 99%

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Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery

Rock¹,

Minatel²,

Marshall³

et al. 2019

Front. Oncol.

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Head and neck squamous cell carcinoma (HNSCC) has a poor survival rate mainly due to late stage diagnosis and recurrence. Despite genomic efforts to identify driver mutations and changes in protein-coding gene expression, developing effective diagnostic and prognostic biomarkers remains a priority to guide disease management and improve patient outcome. Recent reports of previously-unannotated microRNAs (miRNAs) from multiple somatic tissues have raised the possibility of HNSCC-specific miRNAs. In this study, we applied a customized in-silico analysis pipeline to identify novel miRNAs from raw small-RNA sequencing datasets from public repositories. We discovered 146 previously-unannotated sequences expressed in head and neck samples that share structural properties highly characteristic of miRNAs. The combined expression of the novel miRNAs revealed tissue and context-specific patterns. Furthermore, comparison of tumor with non-malignant tissue samples (n = 43 pairs) revealed 135 of these miRNAs as differentially expressed, most of which were overexpressed or exclusively found in tumor samples. Additionally, a subset of novel miRNAs was significantly associated with HPV infection status and patient outcome. A prognostic-model combining novel and known miRNA was developed (multivariate Cox regression analysis) leading to an improved death and relapse risk stratification (log rank p < 1e-7). The presence of these miRNAs was corroborated both in an independent dataset and by RT-qPCR analysis, supporting their potential involvement in HNSCC. In this study, we report the discovery of 146 novel miRNAs in head and neck tissues and demonstrate their potential biological significance and clinical relevance to head and neck cancer, providing a new resource for the study of HNSCC.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery

Rock¹,

Minatel²,

Marshall³

et al. 2019

Front. Oncol.

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“…Furthermore, past efforts to identify human miRNAs have typically prioritized those that are highly expressed across multiple tissues 17 . MiRNA discovery efforts that focused on individual tissues have successfully identified novel, tissue-specific miRNAs that had previously been overlooked 18 , 19 , but the placenta has yet to be studied in this fashion. As a resource for future placental biology investigations, we have profiled and quantified the expression of annotated sncRNAs and determined the expression pattern of novel (previously-unannotated) miRNAs within the human placenta.…”

Section: Background and Summarymentioning

confidence: 99%

Profiling the small non-coding RNA transcriptome of the human placenta

Martínez

Cohn²,

Telkar

et al. 2021

Sci Data

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Proper functioning of the human placenta is critical for maternal and fetal health. While microRNAs (miRNAs) are known to impact placental gene expression, the effects of other small non-coding RNAs (sncRNAs) on the placental transcriptome are not well-established, and are emerging topics in the study of environmental influence on fetal development and reproductive health. Here, we assembled a cohort of 30 placental chorionic villi samples of varying gestational ages (M ± SD = 23.7 ± 11.3 weeks) to delineate the human placental sncRNA transcriptome through small RNA sequence analysis. We observed expression of 1544 sncRNAs, which include 48 miRNAs previously unannotated in humans. Additionally, 18,003 miRNA variants (isomiRs) were identified from the 654 observed miRNA species. This characterization of the term and pre-term placental sncRNA transcriptomes provides data fundamental to future investigations of their regulatory functions in the human placenta, and the baseline expression pattern needed for identifying changes in response to environmental factors, or under disease conditions.

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“…Initial miRNA-identification projects that have dominated the miRNA literature, including publicly accessible databases such as miRBase, emphasize abundant and conserved sequences [9]. There has been a recent push to identify previously unannotated miRNAs that are highly organ-specific, which has expanded the known miRNA transcriptome [9,10,11,12]. Similar to past miRNA-identification projects, these organ-specific analyses rely upon algorithms such as miRDeep2, but they do not concern themselves with sequence conservation between different tissues, and impose less stringent cut-offs on the expression level, which has allowed them to discover miRNAs missed by earlier investigations [9,10,11,12].…”

Section: Introductionmentioning

confidence: 99%

“…There has been a recent push to identify previously unannotated miRNAs that are highly organ-specific, which has expanded the known miRNA transcriptome [9,10,11,12]. Similar to past miRNA-identification projects, these organ-specific analyses rely upon algorithms such as miRDeep2, but they do not concern themselves with sequence conservation between different tissues, and impose less stringent cut-offs on the expression level, which has allowed them to discover miRNAs missed by earlier investigations [9,10,11,12]. The discovery of these novel organ-specific miRNAs has prompted us to reevaluate the raw-sequence data generated by TCGA to identify novel miRNAs in order to upgrade the GA transcriptome and build a new resource for miRNA-based biomarker and therapeutic discovery in this difficult-to-treat cancer.…”

Section: Introductionmentioning

confidence: 99%

Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery

Pewarchuk

Barros-Filho

Minatel

et al. 2019

IJMS

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Recent studies have uncovered microRNAs (miRNAs) that have been overlooked in early genomic explorations, which show remarkable tissue- and context-specific expression. Here, we aim to identify and characterize previously unannotated miRNAs expressed in gastric adenocarcinoma (GA). Raw small RNA-sequencing data were analyzed using the miRMaster platform to predict and quantify previously unannotated miRNAs. A discovery cohort of 475 gastric samples (434 GA and 41 adjacent nonmalignant samples), collected by The Cancer Genome Atlas (TCGA), were evaluated. Candidate miRNAs were similarly assessed in an independent cohort of 25 gastric samples. We discovered 170 previously unannotated miRNA candidates expressed in gastric tissues. The expression of these novel miRNAs was highly specific to the gastric samples, 143 of which were significantly deregulated between tumor and nonmalignant contexts (p-adjusted < 0.05; fold change > 1.5). Multivariate survival analyses showed that the combined expression of one previously annotated miRNA and two novel miRNA candidates was significantly predictive of patient outcome. Further, the expression of these three miRNAs was able to stratify patients into three distinct prognostic groups (p = 0.00003). These novel miRNAs were also present in the independent cohort (43 sequences detected in both cohorts). Our findings uncover novel miRNA transcripts in gastric tissues that may have implications in the biology and management of gastric adenocarcinoma.

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Previously undescribed thyroid-specific miRNA sequences in papillary thyroid carcinoma

Cited by 8 publications

References 20 publications

Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery

Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery

Profiling the small non-coding RNA transcriptome of the human placenta

Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery

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