Role of miRNA-19a in Cancer Diagnosis and Poor Prognosis

Ardizzone, Alessio; Calabrese, Giovanna; Campolo, Michela; Filippone, Alessia; Giuffrida, Dario; Esposito, Francesca; Colarossi, Cristina; Cuzzocrea, Salvatore; Esposito, Emanuela; Paterniti, Irene

doi:10.3390/ijms22094697

Cited by 34 publications

(18 citation statements)

References 128 publications

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“…MicroRNAs (miRNAs) are 19-24-nucleotide-(nt-) long noncoding, single-stranded, small RNAs, which bind to target mRNAs to regulate gene expression [5]. It is reported that miRNAs are involved in various physiological processes including cell proliferation, differentiation, apoptosis, tissue invasion and migration, and angiogenesis [6][7][8]. Li et al found that miR-202-3p inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells through lowering of the matrix metalloproteinase-1 (MMP-1) [9].…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Analysis of mRNAs and miRNAs for Identifying Potential Biomarkers in Lung Adenosquamous Carcinoma

Nie

Gong

Zhu

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Lung adenosquamous carcinoma (LASC) is a special type of lung cancer. LASC is a malignant tumor with strong aggressiveness and a poor prognosis. Previous studies have revealed that microRNAs (miRNAs) are widely involved in the development of tumors by targeting mRNA. This study is aimed at identifying the key mRNAs and miRNAs of LASC and constructing miRNA-mRNA networks for deeply comprehending the latent molecular mechanisms. Methods. mRNA dataset (GSE51852) and miRNA dataset (GSE51853) were extracted and downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were picked out by the GEO2R web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were conducted in the DAVID database. The protein-protein interaction (PPI) network was performed and analyzed by using the STRING database and Cytoscape software, respectively. TransmiR v2.0 was applied to predict potential transcription factors of miRNAs. The target genes of DEMs were predicted in the miRWalk database. Results. In comparison to normal tissues, a total of 1458 DEGs (511 upregulated and 947 downregulated) and 13 DEMs (5 upregulated and 8 downregulated) were screened out in LASC tissues. The PPI network of the DEGs displayed five key modules and seventeen hub genes. Six target genes of the DEMs were predicted, and five essential miRNA-mRNA regulatory pairs were established. Ensuingly, CENPF, one of the target genes, was also the hub genes of GSE51852, which was obtained from MCODE and cytoHubba and regulated by hsa-miR-205. Conclusions. We constructed the miRNA-mRNA regulatory pairs, which are helpful to study the potential regulatory mechanisms and find out promising diagnosis biomarkers and therapeutic targets for LASC.

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Section: Introductionmentioning

confidence: 99%

Bioinformatics Analysis of mRNAs and miRNAs for Identifying Potential Biomarkers in Lung Adenosquamous Carcinoma

Nie

Gong

Zhu

et al. 2022

Computational and Mathematical Methods in Medicine

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“…A total of 20 miRNAs were identified as potential targets of LINC01087 (Analysis 3— Figure 3 , Table S12 ). Most of them had already been involved in carcinogenesis, such as miR-19a-3p and miR-181-5p [ 49 , 50 ]. Furthermore, 4 of the 20 miRNAs belonged to the let-7 miRNA family (i.e., hsa-let-7a-5p, hsa-let-7d-5p, hsa-let-7e-5p, hsa-miR-98-5p).…”

Section: Resultsmentioning

confidence: 99%

Systematic Investigation of the Diagnostic and Prognostic Impact of LINC01087 in Human Cancers

Palma

Carbonnier

Salvatore

et al. 2022

Cancers

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(1) Background: Long non-coding RNAs may constitute epigenetic biomarkers for the diagnosis, prognosis, and therapeutic response of a variety of tumors. In this context, we aimed at assessing the diagnostic and prognostic value of the recently described long intergenic non-coding RNA 01087 (LINC01087) in human cancers. (2) Methods: We studied the expression of LINC01087 across 30 oncological indications by interrogating public resources. Data extracted from the TCGA and GTEx databases were exploited to plot receiver operating characteristic curves (ROC) and determine the diagnostic performance of LINC01087. Survival data from TCGA and KM-Plotter directories allowed us to graph Kaplan–Meier curves and evaluate the prognostic value of LINC01087. To investigate the function of LINC01087, gene ontology (GO) annotation and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed. Furthermore, interactions between LINC01087 and both miRNA and mRNA were studied by means of bioinformatics tools. (3) Results: LINC01087 was significantly deregulated in 7 out of 30 cancers, showing a predominant upregulation. Notably, it was overexpressed in breast (BC), esophageal (ESCA), and ovarian (OV) cancers, as well as lung squamous cell carcinoma (LUSC), stomach adenocarcinoma (STAD), and uterine carcinosarcoma (UCS). By contrast, LINC01087 displayed downregulation in testicular germ cell tumors (TGCT). ROC curve analyses identified LINC01087 as a potential diagnostic indicator in BC, ESCA, OV, STAD, and TGCT. Moreover, high and low expression of LINC01087 predicted a favorable prognosis in BC and papillary cell carcinoma, respectively. In silico analyses indicated that deregulation of LINC01087 in cancer was associated with a modulation of genes related to ion channel, transporter, and peptide receptor activity. (4) Conclusions: the quantification of an altered abundance of LINC01087 in tissue specimens might be clinically useful for the diagnosis and prognosis of some hormone-related tumors, including BC, OV, and TGCT, as well as other cancer types such as ESCA and STAD. Moreover, our study revealed the potential of LINC01087 (and perhaps other lncRNAs) to regulate neuroactive molecules in cancer.

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“…The overexpression of TGF-β in tumor cells exerts dual effects: regulating the expression of PD-L1 and VEGF and affecting biomarkers associated with the modulation of immune response and evasion, including Foxp3/Treg, MDSC, Th1/Th2 balance, and macrophage cells [ 9 , 10 , 17 , 18 , 19 , 49 , 56 , 57 , 58 ]. HIFs and TGF-β are biomarkers associated with the expression of the AXL gene, which is highly overexpressed in tumors with a loss of VHL function and is associated with a poor response to biologically targeted molecules [ 59 , 60 , 61 , 62 , 63 ]. Based on published data generated by others and data generated in our laboratory, Figure 4 is presented to illustrate the potential role of miR-210, miR-155, TGF-β, and HIFs individually or collectively in the regulation of multiple targets.…”

Section: Discussionmentioning

confidence: 99%

“…The data generated in the nine ccRCC cell lines and in the six biopsies showed that miR-17 and miR-19a were downregulated, while miR-34a was upregulated in cell lines with and without sarcomatoid differentiation and downregulated in the six ccRCC tumor biopsies. miR-17, -19a, and -34a were identified to function either as tumor suppressors or as oncogenes [ 49 , 53 , 63 , 68 , 69 , 70 ]. The function of these genes is likely determined by tumor types, cancer stage, and the relative expression levels of these miRs.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets

Swearson

Rataan

Eliason

et al. 2022

IJMS

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This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines—RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL—and in the four ccRCC with sarcomatoid differentiation—RCJ41T1, RCJ41T2, RCJ41M, and UOK-127—indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression. In the one chromophobe renal cell carcinoma cell line, namely, UOK-276 with sarcomatoid differentiation, and expressing tumor suppressor gene TP53, miR-34a, which is a tumor suppressor gene, was expressed at higher levels than miR-210, -155, -17, and -19a. The pilot results generated in six tumor biopsies with matching normal kidney tissues indicated that while the expression of miR-17 and -19a were similar to the normal tissue expression profile, miR-210, -155, -and 34a were expressed at a higher level. To confirm that differences in the expression levels of the five miRs in the six tumor biopsies were statistically significant, the acquisition of a larger sample size is required. Data previously generated in ccRCC cell lines demonstrating that miR-210, miR-155, and HIFs are druggable targets using a defined dose and schedule of selenium-containing molecules support the concept that simultaneous and concurrent downregulation of miR-210, miR-155, and HIFs, which regulate target genes associated with increased tumor angiogenesis and drug resistance, may offer the potential for the development of a novel mechanism-based strategy for the treatment of patients with advanced ccRCC.

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Role of miRNA-19a in Cancer Diagnosis and Poor Prognosis

Cited by 34 publications

References 128 publications

Bioinformatics Analysis of mRNAs and miRNAs for Identifying Potential Biomarkers in Lung Adenosquamous Carcinoma

Bioinformatics Analysis of mRNAs and miRNAs for Identifying Potential Biomarkers in Lung Adenosquamous Carcinoma

Systematic Investigation of the Diagnostic and Prognostic Impact of LINC01087 in Human Cancers

MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets

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