miR-193a-3p inhibition of the Slug activator PAK4 suppresses non-small cell lung cancer aggressiveness via the p53/Slug/L1CAM pathway

Liu, Xincheng; Min, Shengping; Wu, Nan; Liu, Hongli; Wang, Tao; Li, Wei; Shen, Yuanbing; Zhao, Chengling; Wang, Hongtao; Qian, Zhi‐Gang; Xu, Huanbai; Chen, Yuqing; Wang, Xiaojing

doi:10.1016/j.canlet.2019.01.027

Cited by 36 publications

(31 citation statements)

References 35 publications

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“…MiR-193a-3p is reported as a tumor suppressor in many types of cancers. It inhibits the migration and invasiveness of NSCLC [26]. In colorectal cancer, miR-193a-3p inhibited cell proliferation and promoted the apoptosis [27].…”

Section: Discussionmentioning

confidence: 99%

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WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

Tian

Hong

et al. 2020

Preprint

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Abstract Background:Mitogen-inducible gene 6 (Mig-6) is a tumor suppressor gene that plays an important role in many types of cancers by interacting with EGFR. Thus far, little is known about the molecular mechanism of Mig-6 in hepatocellular carcinoma (HCC). Also, the relationship between Mig-6 and miRNAs needs to be elucidated. Therefore, this study first aimed to find whether Mig-6 could promote apoptosis and inhibition of the flux of autophagy by its downstream miRNA in HCC cell lines. Methods: Two cell lines, HepG2and HLE, were used in this study. Mig-6 overexpression and knockdown models , miR-193a mimics and inhibitors models,were established. MiRNA microarray profiling were used to verified Mig-6 regulated- miRNA. Real-time PCR, Western blot analysis were carried out to detect RNA and protein expression.Evaluation of fluorescent LC3 puncta and cell fow cytometer assay were used to test the autophagy and apoptosis respectively. Results: Mig-6 induced the apoptosis and reduced the autophagy of HCC cell lines. MiR-193a-3p is a Mig-6-regulated miRNA in Mig-6 overexpression model, and miR-193a-3p affected the apoptosis and autophagy of HCC cells by regulating the expression of TGF-β2. Additionally, the relationship between Mig-6 and transforming growth factor TGF-β2 was explored in depth for the first time.Conclusion:These findings revealed an important regulatory axis Mig-6/miR-193a-3p/TGF-β2 in the apoptosis and autophagy of HCC cells, providing a novel insight into the therapeutic target in HCC.

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Section: Discussionmentioning

confidence: 99%

“…Numerous targets of miR-193a-3p have been reported [26,28,32,33]. In this study, the TargetScan, miRNA.ORG, and miRDB software were used for the prediction of target genes.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

Tian

Hong

et al. 2020

Preprint

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“…Recently research has reported the inhibitory effect of miR-193-3p in a variety of tumors. In 2019, Liu et al (2019) found that a low level of miR-193a-3p expression was related to the increased expression of p21-activated kinase 4 (PAK4), p-Slug, and L1 cell adhesion molecule (L1CAM) in non-small cell lung cancer (NSCLC) and that miR-193a-3p inhibited the metastasis of NSCLC by repressing PAK4, p-Slug, and L1CAM. Through MTT assay and cell colony formation experiments, Yu et al (2019) showed that miR-193a-3p was downregulated in colorectal cancer cells, while miR-193a-3p's inhibitors promoted the proliferation and invasion of rectal cells.…”

Section: Discussionmentioning

confidence: 99%

“…MiR-133b promotes cell proliferation and metastasis in HCC by regulating splicing factor 3b subunit 4 (SF3B4) (Liu et al, 2018b). MiR-3650 suppresses HCC migration and epithelial-mesenchymal transition (EMT) by directly targeting neurofascin (Wu et al, 2019). could inhibit HCC invasion and metastasis (Liu et al, 2018a;Lou et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-193a-3p is involved in the pathogenesis of hepatocellular carcinoma by targeting CCND1

Wang

Huang

et al. 2020

PeerJ

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Background Hepatocellular carcinoma (HCC) is the second-highest cause of malignancy-related death worldwide, and many physiological and pathological processes, including cancer, are regulated by microRNAs (miRNAs). miR-193a-3p is an anti-oncogene that plays an important part in health and disease biology by interacting with specific targets and signals. Methods In vitro assays were performed to explore the influences of miR-193a-3p on the propagation and apoptosis of HCC cells. The sequencing data for HCC were obtained from The Cancer Genome Atlas (TCGA), and the expression levels of miR-193a-3p in HCC and non-HCC tissues were calculated. The differential expression of miR-193a-3p in HCC was presented as standardized mean difference (SMD) with 95% confidence intervals (CIs) in Stata SE. The impact of miR-193a-3p on the prognoses of HCC patients was determined by survival analysis. The potential targets of miR-193a-3p were then predicted using miRWalk 2.0 and subjected to enrichment analyses, including Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Protein-Protein Interaction (PPI) network analysis. The interaction between miR-193a-3p and one predicted target, Cyclin D1 (CCND1), was verified by dual luciferase reporter assays and Pearson correlation analysis. Results MiR-193a-3p inhibited the propagation and facilitated the apoptosis of HCC cells in vitro. The pooled SMD indicated that miR-193a-3p had a low level of expression in HCC (SMD: −0.88, 95% CI [−2.36 −0.59]). Also, HCC patients with a higher level of miR-193a-3p expression tended to have a favorable overall survival (OS: HR = 0.7, 95% CI [0.43–1.13], P = 0.14). For the KEGG pathway analysis, the most related pathway was “proteoglycans in cancer”, while the most enriched GO term was “protein binding”. The dual luciferase reporter assays demonstrated the direct interaction between miR-193a-3p and CCND1, and the Pearson correlation analysis suggested that miR-193a-3p was negatively correlated with CCND1 in HCC tissues (R = − 0.154, P = 0.002). Conclusion miR-193a-3p could suppress proliferation and promote apoptosis by targeting CCND1 in HCC cells. Further, miR-193a-3p can be used as a promising biomarker for the diagnosis and treatment of HCC in the future.

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“…Previously, Xie et al reported that compared with normal brain tissue, Cyr61 is highly expressed in 66 cases of primary glioma, and Cyr61 expression is significantly related to tumor grade and patient survival [24]; CCND1, as an oncogene [25], is highly expressed in glioma, breast, and bladder cancer; the expression level of CCND1 is related to the malignant degree of tumors and has the effect of regulating the growth and proliferation of cancer cells [26]; Vimentin can reduce the expression of cell surface adhesion factors, thereby promoting the occurrence of cell migration and invasion. It is highly expressed in a variety of cancer tissues, especially in cancers with metastasis [27]; Slug originated from the neural crest and has been reported to be involved in regulating tumor cell invasion, migration, cell cycle, and other activities [28]. In this study, qPCR and Western blotting experiments were performed to demonstrate that CPP treatment of U251 can cause the downregulation of mRNA and protein expression levels of Cyr61, CCND1, Vimentin, and Slug to different degrees, suggesting that CPP plays critical roles in regulating the proliferation, apoptosis, migration, and invasion of gliomas through inhibiting the expression of GSK3β/βcatenin downstream oncogenes Cyr61, CCND1, Vimentin, and Slug.…”

Section: Discussionmentioning

confidence: 99%

Cyclocarya paliurus Polysaccharide Inhibits Glioma Cell U251 Proliferation, Migration, and Invasion and Promotes Apoptosis via the GSK3β/β-Catenin Signaling Pathway

Guo

et al. 2020

International Journal of Polymer Science

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Objective. To investigate the effects of Cyclocarya paliurus polysaccharide (CPP) on the proliferation, migration, invasion, and apoptosis of human glioma U251 cells and further explore the underlying mechanism. Methods. U251 cells were cultured in vitro and treated with various concentrations (25, 50, 75, 100, 125, and 150 μmol/L) of CPP for 24, 48, and 72 h. Cell counting kit-8 was used to detect the activity of cell proliferation. Wound-healing assay, Transwell assay, and flow cytometry were used to measure the effects of CPP on the migration, invasion, and apoptosis of U251 cells, respectively. Western blotting was used to determine the protein expression involved in the GSK3β/β-catenin signaling pathway and its downstream genes related to proliferation, migration, invasion, and apoptosis including Cyr61, CCND1, Vimentin, and Slug. Meanwhile, qRT-PCR was used to detect the mRNA levels of Cyr61, CCND1, Vimentin, and Slug. Results. We found that CPP not only could inhibit the proliferation, migration, and invasion of U251 cells but also promote its apoptosis in vitro. Besides, CPP could significantly inhibit the phosphorylation and decrease the protein levels of GSK3 β at ser9 site (p<0.05), and thus increasing the phosphorylation of β-Catenin at ser33/37 site (p<0.05), resulting in β-Catenin degradation. In addition, we also found that CPP could downregulate the mRNA (p<0.05) and protein expression (p<0.05) of downstream genes of GSK3 β/β-catenin signaling pathway including Cyr61, CCND1, Vimentin, and Slug, which are related to proliferation, migration, invasion, and apoptosis. Conclusion. CPP could inhibit the expression of GSK3β, promote the degradation of β-catenin, and downregulate the levels of GSK3β/β-catenin downstream genes including Cyr61, CCND1, Vimentin, and Slug, which regulate the proliferation, migration, invasion, and apoptosis of glioma cells.

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miR-193a-3p inhibition of the Slug activator PAK4 suppresses non-small cell lung cancer aggressiveness via the p53/Slug/L1CAM pathway

Cited by 36 publications

References 35 publications

WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

Downregulation of miR-193a-3p is involved in the pathogenesis of hepatocellular carcinoma by targeting CCND1

Cyclocarya paliurus Polysaccharide Inhibits Glioma Cell U251 Proliferation, Migration, and Invasion and Promotes Apoptosis via the GSK3β/β-Catenin Signaling Pathway

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