scholarly journals MiR-142-3p could serve as a potential biomarker for individualized treatment of solitary and multiple leiomyomas

2020 ◽  
Author(s):  
Luqi Xue ◽  
E Yang ◽  
Zhengyu Li ◽  
Jinhai Gou ◽  
Dan Nie ◽  
...  

Abstract Background The pathogenesis and clinical behaviors between solitary leiomyoma (SL) and multiple leiomyomas (ML) vary, which lead to the difference in management for childbearing-aged patients. Herein, we aim to find the potential miRNA biomarkers for optimizing the individualized management between SL and ML. Methods A microarray analysis was conducted to screen out the potentially dysregulated miRNAs. Target genes and signaling pathway potentially involved in UL pathogenesis were predicted by bioinformatics. The effect of miRNA was examined by Cell Counting Kit-8 proliferation assay and qRT-PCR after transfection of miRNA mimics Results The top 5 differentially expressed miRNAs, Wnt signalling pathway and its two central molecules APC and CTNNB1 were screened out according to microarray analysis and bioinformatics. MiR-142-3p was selected for further exploration. In validation of qRT-PCR, MiR-142-3p was significantly upregulated in SL, while downregulated in ML, CTNNB1 and sequencing target AXIN-2 were expressed at higher level in ML than SL. Overexpression of MiR-142-3p resulted in lower transcription level of CTNNB1 and AXIN-2, and lower cell proliferation level. Conclusions MiR-142-3p may be involved in the development of SL and ML by interacting with CTNNB1 and AXIN-2 through Wnt signaling pathway. MiR-142-3p could serve as a potential biomarker for individualized treatment between SL and ML in the future.

2020 ◽  
Author(s):  
Luqi Xue ◽  
E Yang ◽  
Zhengyu Li ◽  
Jinhai Gou ◽  
Dan Nie ◽  
...  

Abstract Background: The pathogenesis and clinical behaviors between solitary leiomyoma (SL) and multiple leiomyomas (ML) vary, which lead to the difference in management for childbearing-aged patients. Herein, we aim to find the potential miRNA biomarkers for optimizing the individualized management between SL and ML.Methods: A microarray analysis was conducted to screen out the potentially dysregulated miRNAs. Target genes and signaling pathway potentially involved in UL pathogenesis were predicted by bioinformatics. The effect of miRNA was examined by Cell Counting Kit-8 proliferation assay and qRT-PCR after transfection of miRNA mimicsResults: The top 5 differentially expressed miRNAs, Wnt signalling pathway and its two central molecules APC and CTNNB1 were screened out according to microarray analysis and bioinformatics. MiR-142-3p was selected for further exploration. In validation of qRT-PCR, MiR-142-3p was significantly upregulated in SL, while downregulated in ML, CTNNB1 and sequencing target AXIN-2 were expressed at higher level in ML than SL. Overexpression of MiR-142-3p resulted in lower transcription level of CTNNB1 and AXIN-2, and lower cell proliferation level.Conclusions: MiR-142-3p may be involved in the development of SL and ML by interacting with CTNNB1 and AXIN-2 through Wnt signaling pathway. MiR-142-3p could serve as a potential biomarker for individualized treatment between SL and ML in the future.


2020 ◽  
Author(s):  
Luqi xue ◽  
E Yang ◽  
Jinhai Gou ◽  
Dan Nie ◽  
Tao Yi ◽  
...  

Abstract Background The pathogenesis and clinical behaviors between solitary uterine leiomyoma (SUL) and multiple uterine leiomyomas (MUL) vary, which lead to the difference in management for childbearing-aged patients. Herein, we aim to find the potential miRNAs involved in the development of SUL and MUL. Results The top 5 differentially expressed miRNAs, Wnt signalling pathway and its two central molecules APC and CTNNB1 were screened out according to microarray analysis and bioinformatics. MiR-142-3p was selected for further exploration. In validation of qRT-PCR, MiR-142-3p was significantly upregulated in SUL, while downregulated in MUL, CTNNB1 and sequencing target AXIN-2 were expressed at higher level in MUL than SUL. Overexpression of MiR-142-3p resulted in lower transcription level of CTNNB1 and AXIN-2, and lower cell proliferation level. Conclusions MiR-142-3p may be involved in the development of SUL and MUL by interacting with CTNNB1 and AXIN-2 through Wnt signaling pathway. MiR-142-3p could serve as a potential biomarker for individualized treatment between SUL and MUL in the future.


Author(s):  
Lian Zhao ◽  
San-li Shi ◽  
Wan-liang Guo

IntroductionPancreaticobiliary maljunction (PBM) leads to higher rates of complications, including cholangitis,pancreatitis, and malignancies. The present study was to investigat the expression profile of long non-coding RNAs (lncRNAs) and their potential role as biomarkers in children with pancreaticobiliary maljunction.Material and methodsThe differential expression of lncRNAs and mRNAs from 15 pediatric patients with pancreaticobiliary maljunction and 15 control subjects were analyzed using a commercial microarray and validated with qRT-PCR. The potential biological functions of differentially expressed genes were explored based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The ability of potential lncRNA biomarkers to predict pancreaticobiliary maljunction was assessed based on the area under the receiver operating characteristic curve (AUC).ResultsThere were 2915 mRNAs and 173 lncRNAs upregulated, and 2121 mRNAs and 316 lncRNAs downregulated in pancreaticobiliary maljunction cases compared to controls. The enriched Gene Ontology categories associated with differentially expressed mRNAs were extracellular matrix, extracellular region, and kinetochore. The most enriched Kyoto Encyclopedia pathway was protein digestion and absorption, which has been associated with cancer and PI3K-Akt signaling. Analysis of cis- and trans-target genes predicted that a single lncRNA was able to regulate several mRNAs. The qRT-PCR results for NR_110876, NR_132344, XR_946886, and XR_002956345 were consistent with the microarray results, and the difference was statistically significant for NR_132344, XR_946886, and XR_002956345 (p < 0.05). AUC was significant only for XR_946886 (0.837, p < 0.001).ConclusionsOur results implicate lncRNAs in common bile duct pathogenesis in pancreaticobiliary maljunction, and they identify XR_946886 as a potential biomarker for the disease.


2000 ◽  
Vol 14 (14) ◽  
pp. 1741-1749 ◽  
Author(s):  
Ken-ichi Tago ◽  
Tsutomu Nakamura ◽  
Michiru Nishita ◽  
Junko Hyodo ◽  
Shin-ichi Nagai ◽  
...  

Wnt signaling has an important role in both embryonic development and tumorigenesis. β-Catenin, a key component of the Wnt signaling pathway, interacts with the TCF/LEF family of transcription factors and activates transcription of Wnt target genes. Here, we identify a novel β-catenin-interacting protein, ICAT, that was found to inhibit the interaction of β-catenin with TCF-4 and represses β-catenin–TCF-4-mediated transactivation. Furthermore, ICAT inhibited Xenopus axis formation by interfering with Wnt signaling. These results suggest that ICAT negatively regulates Wnt signaling via inhibition of the interaction between β-catenin and TCF and is integral in development and cell proliferation.


2018 ◽  
Vol 50 (4) ◽  
pp. 1398-1413 ◽  
Author(s):  
Min Li ◽  
Chun-Xia Ren ◽  
Jian-Mei Zhang ◽  
Xiao-Yan Xin ◽  
Teng Hua ◽  
...  

Background/Aims: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC. Methods: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice. Results: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development. Conclusion: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway.


2008 ◽  
Vol 105 (40) ◽  
pp. 15417-15422 ◽  
Author(s):  
Jennifer A. Kennell ◽  
Isabelle Gerin ◽  
Ormond A. MacDougald ◽  
Ken M. Cadigan

Wnt signaling plays many important roles in animal development. This evolutionarily conserved signaling pathway is highly regulated at all levels. To identify regulators of the Wnt/Wingless (Wg) pathway, we performed a genetic screen in Drosophila. We identified the microRNA miR-8 as an inhibitor of Wg signaling. Expression of miR-8 potently antagonizes Wg signaling in vivo, in part by directly targeting wntless, a gene required for Wg secretion. In addition, miR-8 inhibits the pathway downstream of the Wg signal by repressing TCF protein levels. Another positive regulator of the pathway, CG32767, is also targeted by miR-8. Our data suggest that miR-8 potently antagonizes the Wg pathway at multiple levels, from secretion of the ligand to transcription of target genes. In addition, mammalian homologues of miR-8 promote adipogenesis of marrow stromal cells by inhibiting Wnt signaling. These findings indicate that miR-8 family members play an evolutionarily conserved role in regulating the Wnt signaling pathway.


Lupus ◽  
2021 ◽  
pp. 096120332110614
Author(s):  
Yan Liang ◽  
Ji Zhang ◽  
Wenxian Qiu ◽  
Bo Chen ◽  
Ying Zhou ◽  
...  

Objective Lupus nephritis (LN) is a major end-organ complication of systemic lupus erythematosus (SLE), and the molecular mechanism of LN is not completely clear. Accumulating pieces of evidence indicate the potential vital role of tRNA-derived small RNAs (tsRNAs) in human diseases. Current study aimed to investigate the potential roles of tsRNAs in LN. Methods We herein employed high‐throughput sequencing to screen the expression profiles of tsRNAs in renal tissues of the LN and control groups. To validate the sequencing data, we performed quantitative real-time PCR (qRT-PCR) analysis. Correlational analysis of verified tsRNAs expression and clinical indicators was conducted using linear regression. The potential target genes were also predicted. The biological functions of tsRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results Our findings revealed that the expression profiles of tsRNAs were significantly altered in the kidney tissues from LN patients compared with control. Overall, 160 tsRNAs were significantly dysregulated in the LN group, of which 79 were upregulated, whereas 81 were downregulated. Subsequent qRT-PCR results confirmed the different expression of candidate tsRNAs. Correlation analysis results found that expression of verified tsRNAs were correlated to clinical indicators. The target prediction results revealed that verified tsRNAs might act on 712 target genes. Further bioinformatics analysis uncovered tsRNAs might participate in the pathogenesis of LN through several associated pathways, including cell adhesion molecules, MAPK signaling pathway, PI3K-Akt signaling pathway and B cell receptor signaling pathway. Conclusion This study provides a novel insight for studying the mechanism of LN.


Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1173 ◽  
Author(s):  
Mailin Gan ◽  
Shunhua Zhang ◽  
Yuan Fan ◽  
Ya Tan ◽  
Zhixian Guo ◽  
...  

Cardiac hypertrophy is a common pathological condition and an independent risk factor that triggers cardiovascular morbidity. As an important epigenetic regulator, miRNA is widely involved in many biological processes. In this study, miRNAs expressed in rat hearts that underwent isoprenaline-induced cardiac hypertrophy were identified using high-throughput sequencing, and functional verification of typical miRNAs was performed using rat primary cardiomyocytes. A total of 623 miRNAs were identified, of which 33 were specifically expressed in cardiac hypertrophy rats. The enriched pathways of target genes of differentially expressed miRNAs included the FoxO signaling pathway, dopaminergic synapse, Wnt signaling pathway, MAPK (mitogen-activated protein kinase) signaling pathway, and Hippo signaling pathway. Subsequently, miR-144 was the most differentially expressed miRNA and was subsequently selected for in vitro validation. Inhibition of miR-144 expression in primary myocardial cells caused up-regulation of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The dual luciferase reporter system showed that ANP may be a target gene of miR-144. Long non-coding RNA myocardial infarction associated transcript (LncMIAT) is closely related to heart disease, and here, we were the first to discover that LncMIAT may act as an miR-144 sponge in isoproterenol-induced cardiac hypertrophy. Taken together, these results enriched the understanding of miRNA in regulating cardiac hypertrophy and provided a reference for preventing and treating cardiac hypertrophy.


Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1565
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jiang Hu ◽  
Xiu Liu ◽  
...  

Long non-coding RNAs (lncRNAs) are a kind of non-coding RNA with >200 nucleotides in length. Some lncRNAs have been proven to have clear regulatory functions in many biological processes of mammals. However, there have been no reports on the roles of lncRNAs in ovine mammary gland tissues. In the study, the expression profiles of lncRNAs were studied using RNA-Seq in mammary gland tissues from lactating Small-Tailed Han (STH) ewes and Gansu Alpine Merino (GAM) ewes with different milk yield and ingredients. A total of 1894 lncRNAs were found to be expressed. Compared with the GAM ewes, the expression levels of 31 lncRNAs were significantly up-regulated in the mammary gland tissues of STH ewes, while 37 lncRNAs were remarkably down-regulated. Gene Ontogeny (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the target genes of differentially expressed lncRNAs were enriched in the development and proliferation of mammary epithelial cells, morphogenesis of mammary gland, ErbB signaling pathway, and Wnt signaling pathway. Some miRNA sponges of differentially expressed lncRNAs, reported to be associated with lactation and mammary gland morphogenesis, were found in a lncRNA-miRNA network. This study reveals comprehensive lncRNAs expression profiles in ovine mammary gland tissues, thereby providing a further understanding of the functions of lncRNAs in the lactation and mammary gland development of sheep.


2020 ◽  
Vol 143 (6) ◽  
pp. 533-551 ◽  
Author(s):  
Feiyan Wang ◽  
Lan Luo ◽  
Zhenyang Gu ◽  
Nan Yang ◽  
Li Wang ◽  
...  

<b><i>Background:</i></b> Chronic graft-versus-host disease (cGVHD) remains a major cause of late non-recurrence mortality despite remarkable improvements in the field of allogeneic hematopoietic stem cell transplantation. Although recent studies have found that B-cell receptor (BCR)-activated B cells contribute to pathogenesis in cGVHD, the specific molecular mechanisms of B cells in this process remain unclear. <b><i>Methods:</i></b> In our study, human long noncoding RNA (lncRNA) microarrays and bioinformatic analysis were performed to identify different expressions of lncRNAs in peripheral blood B cells from cGVHD patients compared with healthy ones. The differential expression of lncRNA was confirmed in additional samples by quantitative real-time polymerase chain reaction (qRT-PCR). <b><i>Results:</i></b> The microarray analysis revealed that 106 of 198 differentially expressed lncRNAs were upregulated and 92 were downregulated in cGVHD patients compared with healthy controls. Intergenic lncRNAs accounted for the majority of differentially expressed lncRNAs. A KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the differentially expressed mRNAs, which were coexpressed with lncRNA, between the cGVHD group and the healthy group were significantly enriched in the BCR signaling pathway. Further analysis of the BCR signaling pathway and its coexpression network identified three lncRNAs with the strongest correlation with BCR signaling and cGVHD, as well as a series of protein-coding genes and transcription factors associated with them. The three candidate lncRNAs were further validated in another group of cGVHD patients by qRT-PCR. <b><i>Conclusions:</i></b> This is the first study on the correlation between lncRNA and cGVHD using lncRNA microarray analysis. Our study provides novel enlightenment in exploring the molecular pathogenesis of cGVHD.


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