Knockdown of miR-194-5p inhibits cell proliferation, migration and invasion in breast cancer by regulating the Wnt/β-catenin signaling pathway

Yang, Fei; Xiao, Zhangsheng; Zhang, Songze

doi:10.3892/ijmm.2018.3897

Cited by 34 publications

(34 citation statements)

References 34 publications

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“…In BC, miR‐194‐5p was described as having tumor‐suppressive roles by inhibiting proliferation and migration in vitro and in vivo (Le et al , ). However, a recent paper demonstrated that miR‐194‐5p enhances cell proliferation, migration, and invasion in different BC cell lines via Wnt/β‐catenin pathway regulation (Yang et al , ). These contradicting reports may be a consequence of the multitude of genes and functions that one single miRNA can regulate and of the multiple factors and cellular contexts that influence their expression (Dykxhoorn, ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of circulating miR 802‐5p and miR 194‐5p and upregulation of brain MEF2C along breast cancer brain metastasization

et al. 2020

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Breast cancer brain metastases (BCBMs) have been underinvestigated despite their high incidence and poor outcome. MicroRNAs (miRNAs), and particularly circulating miRNAs, regulate multiple cellular functions, and their deregulation has been reported in different types of cancer and metastasis. However, their signature in plasma along brain metastasis development and their relevant targets remain undetermined. Here, we used a mouse model of BCBM and next‐generation sequencing (NGS) to establish the alterations in circulating miRNAs during brain metastasis formation and development. We further performed bioinformatics analysis to identify their targets with relevance in the metastatic process. We additionally analyzed human resected brain metastasis samples of breast cancer patients for target expression validation. Breast cancer cells were injected in the carotid artery of mice to preferentially induce metastasis in the brain, and samples were collected at different timepoints (5 h, 3, 7, and 10 days) to follow metastasis development in the brain and in peripheral organs. Metastases were detected from 7 days onwards, mainly in the brain. NGS revealed a deregulation of circulating miRNA profile during BCBM progression, rising from 18% at 3 days to 30% at 10 days following malignant cells’ injection. Work was focused on those altered prior to metastasis detection, among which were miR‐802‐5p and miR‐194‐5p, whose downregulation was validated by qPCR. Using targetscan and diana tools, the transcription factor myocyte enhancer factor 2C (MEF2C) was identified as a target for both miRNAs, and its expression was increasingly observed in malignant cells along brain metastasis development. Its upregulation was also observed in peritumoral astrocytes pointing to a role of MEF2C in the crosstalk between tumor cells and astrocytes. MEF2C expression was also observed in human BCBM, validating the observation in mouse. Collectively, downregulation of circulating miR‐802‐5p and miR‐194‐5p appears as a precocious event in BCBM and MEF2C emerges as a new player in brain metastasis development.

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Section: Discussionmentioning

confidence: 99%

Downregulation of circulating miR 802‐5p and miR 194‐5p and upregulation of brain MEF2C along breast cancer brain metastasization

et al. 2020

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“…Downregulation of miR-194 reduces nuclear accumulation of β-catenin and inhibits the Wnt signaling pathway in gastric cancer (35). In addition, the proliferation and infiltration of breast cancer cells are inhibited by knockout of miR-194, which regulates the Wnt/β-catenin signaling pathway (36). Miao et al (37) also revealed that miR-194 targets cadherin 2 (CDH2) to inhibit cell expansion and promote apoptosis in osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis

Zheng

et al. 2020

Exp Ther Med

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The etiology and pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are yet to be fully elucidated; however, mining of disease-related microRNAs (miRNAs/miRs) has improved the understanding of the progression of IPF. The aim of the current study was to screen miRNAs associated with IPF using three mathematical algorithms: One-way ANOVA, least absolute shrinkage and selector operation (LASSO) and support vector machinerecursive feature elimination (SVM-RFE). Using ANOVA, three miRNAs and two miRNAs were selected with opposite expression patterns in moderate and severe IPF, respectively. In total, two algorithms, LASSO and SVM-RFE, were used to perform feature selection of miRNAs. miRNAs from patients were also extracted from formalin-fixed paraffin-embedded tissues and detected using reverse transcription-quantitative PCR (RT-qPCR). The intersection of the three algorithms (ANOVA, LASSO and SVM-RFE) was taken as the final result of the miRNA candidates. Three miRNA candidates, including miR-124, hsa-miR-524-5p and hsa-miR-194 were therefore used as biomarkers. The receiver operating characteristic model demonstrated favorable discrimination between IPF and control groups, with an area under the curve of 78.5%. Moreover, RT-qPCR results indicated that miR-124, hsa-miR-524-5p, hsa-miR-194 and hsa-miR-133a were differentially expressed between patients with IPF and age-matched men without fibrotic lung disease. The target genes of these miRNAs were further predicted and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed. Collectively, the present results suggested that the identified miRNAs associated with IPF may be useful biomarkers for the diagnosis of this disease.

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“…[25][26][27] Interestingly, Yang et al found that miR-194-5p was up-regulated in breast cancer tissues and silence of miR-194-5p inhibited cell proliferation and metastasis via targeting SOX17. 28 Meanwhile, decreased miR-194-5p was implicated in sunitinib resistance in human renal cell carcinoma and paclitaxel resistance in ovarian cancer. 29,30 These studies revealed a complex function and molecular basis of miR-194-5p, yet its role in OSCC still remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

<p>LncRNA PVT1 Enhances Proliferation and Cisplatin Resistance via Regulating miR-194-5p/HIF1a Axis in Oral Squamous Cell Carcinoma</p>

Wang

et al. 2020

OTT

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Background: Oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy. Recent studies have revealed that long non-coding RNA (lncRNA) PVT1 plays important roles in the pathogenesis of various cancers. However, the functional roles of PVT1 in OSCC progression and cisplatin resistance have not been elucidated. Material and Methods: In this study, PVT1 expression level in cisplatin-sensitive and cisplatin-resistant OSCC tissues and cell lines was determined using qRT-PCR. Gain-offunction and loss-of-function assays were performed to explore the biological roles of PVT1 in OSCC cell proliferation and cisplatin resistance. Western blot, luciferase reporter assay and bioinformatics analysis were employed to investigate the underlying mechanism of PVT1 in OSCC progression. Results: Here, we found that PVT1 was frequently up-regulated in cisplatin-resistant tissues and cell lines and strongly correlated with worse overall survival. Functional studies showed that PVT1 promoted OSCC cell proliferation and cisplatin resistance. Mechanistic investigation revealed that PVT1 could positively regulate HIF1a expression via its competing endogenous RNA (ceRNA) activity on miR-194-5p. In addition, miR-194-5p conversely correlated with PVT1 and HIF1a expression in OSCC samples. More importantly, HIF1a knock-down or miR-194-5p overexpression reversed PVT1-induced promotion of OSCC cell proliferation and cisplatin resistance. Conclusion: Our results indicated that PVT1 functions as an oncogene involved in OSCC cell proliferation and cisplatin-resistance and may serve as a novel therapeutic target for OSCC treatment.

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Knockdown of miR-194-5p inhibits cell proliferation, migration and invasion in breast cancer by regulating the Wnt/β-catenin signaling pathway

Cited by 34 publications

References 34 publications

Downregulation of circulating miR 802‐5p and miR 194‐5p and upregulation of brain MEF2C along breast cancer brain metastasization

Downregulation of circulating miR 802‐5p and miR 194‐5p and upregulation of brain MEF2C along breast cancer brain metastasization

Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis

<p>LncRNA PVT1 Enhances Proliferation and Cisplatin Resistance via Regulating miR-194-5p/HIF1a Axis in Oral Squamous Cell Carcinoma</p>

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