Integrated analysis of colorectal cancer microRNA datasets: identification of microRNAs associated with tumor development

Falzone, Luca; Scola, Letizia; Zanghì, Antonio; Biondi, Antonio; Cataldo, Antonio Di; Libra, Massimo; Candido, Saverio

doi:10.18632/aging.101444

Cited by 139 publications

(115 citation statements)

References 68 publications

(49 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…We also studied the possible diagnostic and prognostic value of TSPAN32 expression in PBMC of MS patients, on the course of the disease. The use of whole-genome expression databases has been largely exploited [25][26][27][28] for the characterization of pathogenic pathways and to identify therapeutic targets for a variety of disorders, including immunoinflammatory and autoimmune diseases [29][30][31][32][33][34][35][36], cancer [37][38][39], and has allowed dismantling pathogenetic pathways [40][41][42], along with the identification of novel tailored therapeutic targets [43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

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Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

et al. 2020

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Tetraspanins are a conserved family of proteins involved in a number of biological processes. We have previously shown that Tetraspanin-32 (TSPAN32) is significantly downregulated upon activation of T helper cells via anti-CD3/CD28 stimulation. On the other hand, TSPAN32 is marginally modulated in activated Treg cells. A role for TSPAN32 in controlling the development of autoimmune responses is consistent with our observation that encephalitogenic T cells from myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice exhibit significantly lower levels of TSPAN32 as compared to naïve T cells. In the present study, by making use of ex vivo and in silico analysis, we aimed to better characterize the pathophysiological and diagnostic/prognostic role of TSPAN32 in T cell immunity and in multiple sclerosis (MS). We first show that TSPAN32 is significantly downregulated in memory T cells as compared to naïve T cells, and that it is further diminished upon ex vivo restimulation. Accordingly, following antigenic stimulation, myelin-specific memory T cells from MS patients showed significantly lower expression of TSPAN32 as compared to memory T cells from healthy donors (HD). The expression levels of TSPAN32 was significantly downregulated in peripheral blood mononuclear cells (PBMCs) from drug-naïve MS patients as compared to HD, irrespective of the disease state. Finally, when comparing patients undergoing early relapses in comparison to patients with longer stable disease, moderate but significantly lower levels of TSPAN32 expression were observed in PBMCs from the former group. Our data suggest a role for TSPAN32 in the immune responses underlying the pathophysiology of MS and represent a proof-of-concept for additional studies aiming at dissecting the eventual contribution of TSPAN32 in other autoimmune diseases and its possible use of TSPAN32 as a diagnostic factor and therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

et al. 2020

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“…The PPIA expression level also implied the clinical characteristics of resected lung adenocarcinomas and was correlated with a poor prognosis of lung adenocarcinoma (Nakano et al, 2017).However, the in-depth study of the PPIA overexpression mechanism in CRC was insufficient. Analysis of TCGA miRNA-sequencing data showed that downregulation of hsa-miR-1-3p may be a diagnostic marker of CR and that it was significantly related with the pathological stage (Zhou et al, 2018;Falzone et al, 2018). Therefore, further molecular biology experiments may be able to prove the interaction of the downregulation of hsa-miR-1-3p and the upregulation of PPIA, which is conducive to a better understanding of the CRC posttranscriptional regulation mechanism.…”

Section: Discussionmentioning

confidence: 98%

Post-Transcriptional Dysregulation of microRNA and Alternative Polyadenylation in Colorectal Cancer

et al. 2020

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Background: Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. microRNAs (miRNAs) repress gene expression by binding to complementary sequences in the 3' untranslated region (3'UTR) of target mRNAs. Alternative polyadenylation (APA) are relevant to the variability of the 3'UTR of mRNA. However, the posttranscriptional dysregulation of miRNAs and APA in CRC are poorly understood.Method: In this study, we conducted small RNA sequencing to identify differentially expressed miRNAs (DERs) and their target genes. Function analysis on DER-target genes can explain the regulation roles of miRNAs in CRC. The mutual regulation of miRNAs and APA was analyzed by combining miRNA data to 3'UTR alteration using 3' termini of polyadenylated RNAs sequencing (3T-seq) technique, and this was validated using TCGA gene expression data.Results: Our results showed 64 significant differentially expressed miRNAs (DERs) in CRC patients. Their target genes were related to cell adhesion and transcription regulation and were prevailingly involved in the CRC-related pathway. Integrative analysis of the miRNA and APA profile revealed 16 DERs were correlated with 12 polyadenylation factors, and six of them were significantly differently expressed in CRC. We also found four DERs that lost binding sites due to APA and showed a positive correlation between the miRNA and gene expression.Conclusion: Our study found that miRNAs regulated APA by modulating key polyadenylation factors, and several miRNAs lost their suppression on mRNA due to APA. Associating this with gene expression may provide some important clues for a deeper study of posttranscriptional cellular regulation and biomarker research in CRC. Our data provided the first evidence that the interaction between miRNAs and APA associated with gene expression could serve as biomarkers for CRC, suggesting that hsa-miR-133a-Frontiers in Genetics | www.frontiersin.org 3p and MLEC, hsa-miR-145-5p and SET, hsa-miR-1-3p and PPIA, and hsa-miR-378d and YY1 might be novel and potential biomarkers in improving the diagnosis of CRC.

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“…These biomarkers can be used for early diagnosis, individualized treatment and prognosis of colorectal cancer [36]. For example, hsa-mir-183-5p and hsa-mir-21-5p [37], hsa-mir-30a [38], hsa-mir-96 [39], hsa-mir-21 [40] for diagnosis of colorectal cancer. And hsa-mir-143 and hsa-mir-145 for prognosis of colorectal cancer [41].…”

Section: Discussionmentioning

confidence: 99%

“…CEA, CA19-9 and CA24-2 were measured routinely by flow fluorescence method with Quantitative Detection Kit for Tumor Markers (Tellgen Life Science, Shanghai, China). Critical value of CEA, CA19-9 and CA24-2 was 5.00ng/mL, 37.00U/mL and 20.00U/mL. The results were considered positive when any of the markers were positive, and negative when all of the markers were negative.…”

Section: Sample Preparation and Tumor Markers Detectionmentioning

confidence: 99%

Clinical Diagnostic Value for Colorectal cancer Based on Serum CEA, CA24-2 and CA19-9

Rao

Huang

et al. 2020

Preprint

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Background To explore the clinical value of a combined detection of serum concentration of carcinoembryonic antigen (CEA), carbohydrate antigen 24-2 (CA24-2), and carbohydrate antigen 19-9 (CA19-9) for colorectal cancer (CRC).Methods The levels of serum tumor markers (CEA, CA24-2 and CA19-9) and clinicopathologic features in patients with colorectal cancer in Meizhou People's Hospital were evaluated. In addition, KRAS/NRAS, PIK3CA and BRAF mutations were detected in some patients with colorectal cancer.Results A total of 2,281 patients (1,420 males and 861 females) were recruited in the study, included 1,578 colorectal cancer patients and 703 controls. The levels of CEA, CA24-2 and CA19-9 in colorectal cancer group was significantly higher than control group. The sensitivities of three individual markers were lower than 30%, which individual sensitivity of the tumor markers sorted in descending order were CEA> CA19-9> CA24-2. The specificities of three individual markers were more than 92%, and the specificity sorted in descending order were CA24-2> CA19-9> CEA. The prediction equation excluding the risk of colorectal cancer was. Probability (normal) = Exp (-5.47 -0.28CEA -0.11 CA242 + 0.001 CA199)/ (1+ Exp (-5.47 -0.28CEA -0.11 CA242 + 0.001 CA199)). There were no significant differences in age, gender, histology type, differentiation, depth of invasion and TNM stage between mutations in KRAS/NRAS , BRAF and PIK3CA genes or not, respectively.Conclusions Serum CEA, ca24-2, and ca19-9 are valuable noninvasive indicators for the detection and screening of patients with early colon cancer. We need to look for other, more sensitive tumor markers.

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Integrated analysis of colorectal cancer microRNA datasets: identification of microRNAs associated with tumor development

Cited by 139 publications

References 68 publications

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

Post-Transcriptional Dysregulation of microRNA and Alternative Polyadenylation in Colorectal Cancer

Clinical Diagnostic Value for Colorectal cancer Based on Serum CEA, CA24-2 and CA19-9

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