High-Throughput Sequencing of miRNAs Reveals a Tissue Signature in Gastric Cancer and Suggests Novel Potential Biomarkers

Darnet, Sylvain; Moreira, Fabiano Cordeiro; Hamoy, Igor; Burbano, Rommel Rodrı́guez; Khayat, André Salim; Cruz, Aline; Magalhães, Leandro; Silva, Artur M. S.; Santos, Sidney Emanuel Batista dos; Demachki, Sâmia; Assumpção, Mônica Baraúna de; Assumpção, Paulo Pimentel de; Ribeiro-dos-Santos, Ândrea

doi:10.4137/bbi.s23773

Cited by 17 publications

(23 citation statements)

References 55 publications

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“…It was demonstrated that hsa‐miR‐135b is up‐regulated in stomach carcinoma tissues . Based on the results obtained in several studies, hsa‐miR‐135b is reported as a potential biomarker of the intestinal‐type of STAD . In our study, hsa‐miR‐196b and hsa‐miR‐135b were also up‐regulated, which was in line with previous reports.…”

Section: Discussionsupporting

confidence: 92%

Identification of key miRNAs and genes associated with stomach adenocarcinoma from The Cancer Genome Atlas database

Liu

Shi

et al. 2018

FEBS Open Bio

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Stomach adenocarcinoma (STAD) is the second leading cause of cancer death and a fuller understanding of its molecular basis is needed to develop new therapeutic targets. mi RNA and mRNA data were downloaded from The Cancer Genome Atlas database, and the differentially expressed mi RNA s and genes were identified. The target genes of differentially expressed mi RNA s were screened by prediction tools. Furthermore, the biological function of these target genes was investigated. Several key mi RNA s and their target genes were selected for validation using quantitative real‐time polymerase chain reaction ( qRT ‐ PCR ). The Gene Expression Omnibus ( GEO ) dataset was used to verify the expression of selected mi RNA s and target genes. The diagnostic value of identified mi RNA s and genes was accessed by receiver operating characteristic analysis. A total of 1248 differentially expressed genes were identified in STAD. Additionally, nine differentially expressed mi RNA s were identified and 160 target genes of these nine mi RNA s were identified via target gene detection. Interestingly, they were remarkably enriched in the calcium signaling pathway and bile secretion. qRT ‐ PCR confirmed the expression of several key mi RNA s and their target genes. The expression levels of hsa‐miR‐145‐3p, hsa‐miR‐145‐5p, ADAM 12 , ACAN , HOXC 11 and MMP 11 in the GEO database were compatible with the bioinformatics results. hsa‐miR‐139‐5p, hsa‐miR‐145‐3p and MMP11 have a potential diagnostic value for STAD. Differential expression of the mature form of mi RNA s (hsa‐miR‐139‐5p, hsa‐miR‐145‐3p, hsa‐miR‐145‐5p and hsa‐miR‐490‐3p) and genes including ADAM 12 , ACAN , HOXC 11 and MMP 11 and calcium and bile secretion signaling pathways may play important roles in the development of STAD.

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Section: Discussionsupporting

confidence: 92%

Identification of key miRNAs and genes associated with stomach adenocarcinoma from The Cancer Genome Atlas database

Liu

Shi

et al. 2018

FEBS Open Bio

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“…MicroRNAs (miRNAs) are small non-coding regulatory RNAs (~23 nucleotides in length) that play a crucial role in the post-transcriptional regulation of gene expression by suppressing target mRNA translation by binding to its 3'untranslated region (UTR) region (10)(11)(12). Therefore, miRNAs can regulate multiple mRNAs to create a complex regulatory network of signaling pathways including oncogene pathways and tumor suppressor pathways, such as the Wnt and PI3K pathways (13)(14)(15)(16).…”

Section: Abnormal Expression Of Mir-135b-5p In Bone Tissue Of Patientmentioning

confidence: 99%

Abnormal expression of miR‑135b‑5p in bone tissue of patients with osteoporosis and its role and mechanism in osteoporosis progression

et al. 2019

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Osteoporosis (OP) is an age-related bone disease occurring worldwide. Osteoporotic fracture is one of the leading causes of disability and death in elderly patients. MicroRNAs (miRNAs/miRs) are key molecular regulatory factors in bone remodeling processes. The present study investigated the expression and mechanism of miR-135b-5p in patients with osteoporosis. The present results suggested that miR-135b-5p was upregulated in bone tissue fragments of patients with osteoporosis compared with the control patients. MC3T3-E1 cells were used to perform osteogenic differentiation induction. Reverse transcription-quantitative PCR and western blot assay were used to detect the mRNA and protein expression levels of the osteogenic markers osteocalcin (OC), Osterix and alkaline phosphatase (ALP). A specific kit was used for detecting ALP activity. The present results indicated that the mRNA expression levels of OC, Osterix and ALP significantly increased on the 7 and 14th day after osteogenic differentiation induction compared with the control group. Protein expression levels of OC, Osterix and ALP also increased on the 7 and 14th day after induction. ALP assay showed that ALP activity was significantly increased on the 7 and 14th day after induction. In addition, the present study found that miR-135b-5p was downregulated in MC3T3-E1 cells 7 and 14 days after osteogenic differentiation induction. The results of TargetScan analysis and dual luciferase reporter gene assay indicated that runt-related transcription factor 2 (RUNX2) was a direct target gene of miR-135b-5p. RUNX2 was upregulated in MC3T3-E1 cells on the 7 and 14th day after induction. Moreover, the present study found that compared with the osteogenic differentiation induction group, miR-135b-5p mimic significantly decreased OC, Osterix and ALP expression, and reduced ALP activity in MC3T3-E1 cells. However, these reductions were reversed following overexpression of RUNX2. The present results showed that miR-135b-5p mimic significantly reduced cell viability in MC3T3-E1 cells and induced cell apoptosis, and these effects were significantly reversed following RUNX2 overexpression. In summary, the present results suggested that miR-135-5p participated in the occurrence and development of osteoporosis via inhibition of osteogenic differentiation and osteoblast growth by targeting RUNX2. The present study suggested a novel potential target that may faciliate the treatment of osteoporosis, and further study is required to examine this possibility.

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“…In order to find more sensitive biomarkers, we focused on 10 miRs with the highest alteration levels in the tissue of UCB patients (Figure 3). Of these 10 miRNAs, we chose 9 miRNAs, hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-4324, hsa-miR-34b-5p, hsa-miR-29c-3p, hsa-miR-135a-3p, and hsa-miR-33b-3p which were previously reported to have an oncogenic or antioncogenic roles [5,[14][15][16][17][18][19][20][21], (Figure 4). Our previous studies found that the expression levels of antitumorigenic miR-145 were significantly lower in surgically resected BC samples and BC cell lines compared to those in normal bladder tissues, thereby miR-145 decreases the Warburg effect by silencing KLF4 [22,23].…”

Section: Disease Markersmentioning

confidence: 99%

A panel of micro-RNA signature as a tool for predicting survival of patients with urothelial carcinoma of the bladder

Inamoto¹,

Takahara²,

Ibuki³

et al. 2017

European Urology Supplements

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Introduction and Objectives. MicroRNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRNAs have been shown to modulate multiple signaling pathways that contribute to BC. To identify a panel of miRNA signature that can predict aggressive phenotype from normal nonaggressive counterpart using miRNA expression levels and to assess the prognostic value of this specific miRNA markers in patients with UCB. Methods. To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UCB, miRNA expression was profiled in patients' samples with an aggressive phenotype or nonaggressive phenotype using 3D-Gene miRNA labeling kit (Toray, Japan). To create a prognostic index model, we used the panel of 9-miRNA signature based on Cancer Genome Atlas (TCGA) data portal (TCGA Data Portal (https://tcgadata.nci.nih.gov/tcga/tcgaHome2.jsp)). miRNA expression data and corresponding clinical data, including outcome and staging information of 84 UCB patients, were obtained. The Kaplan-Meier and log-rank test were performed to quantify the survival functions in two groups. Results. Deregulation of nine miRNAs (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-4324, hsa-miR-34b-5p, hsa-miR-29c-3p, hsa-miR-135a-3p, and hsa-miR-33b-3p) was determined in UCB patients with aggressive phenotype compared with nonaggressive subject. To validate the prognostic power of the nine-signature miRNAs using the TCGA dataset of bladder cancer, the survival status and tumor miRNA expression of all 84 TCGA UCB patients were ranked according to the prognostic score values. Of nine miRNAs, six were associated with high risk (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-4324, hsa-miR-34b-5p, and hsa-miR-135a-3p) and three were shown to be protective (hsa-miR-145-5p, hsa-miR-29c-3p, and hsa-miR-33b-3p). Patients with the high-risk miRNA signature exhibited poorer OS than patients expressing the low-risk miRNA profile (HR = 7.05, p < 0 001). Conclusions. The miRNA array identified nine dysregulated miRNAs from clinical samples. This panel of nine-miRNA signature provides predictive and prognostic value of patients with UCB.

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High-Throughput Sequencing of miRNAs Reveals a Tissue Signature in Gastric Cancer and Suggests Novel Potential Biomarkers

Cited by 17 publications

References 55 publications

Identification of key miRNAs and genes associated with stomach adenocarcinoma from The Cancer Genome Atlas database

Identification of key miRNAs and genes associated with stomach adenocarcinoma from The Cancer Genome Atlas database

Abnormal expression of miR‑135b‑5p in bone tissue of patients with osteoporosis and its role and mechanism in osteoporosis progression

A panel of micro-RNA signature as a tool for predicting survival of patients with urothelial carcinoma of the bladder

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