MicroRNA‐455 suppresses non‐small cell lung cancer through targeting ZEB1

Li, Yingjie; Chen, Ping; Tang, Jian; Zhang, Wen

doi:10.1002/cbin.10584

Cited by 43 publications

(40 citation statements)

References 32 publications

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“…In the present study, miR-200b was upregulated and predicted to target KALRN, suggesting that expression of KALRN may be downregulated by miR-200b, and this downregulation may subsequently promote pneumonia development. A previous study reported that miR-455 suppresses NSCLC by targeting the transcript encoding Zinc finger E-box-binding homeobox 1 (45). This indicates that upregulation of miR-455 may inhibit the development of pneumonia.…”

Section: Discussionmentioning

confidence: 91%

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

Huang¹,

Cong²,

Zhai³

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Pneumonia is a lower respiratory tract infection that causes dramatic mortality worldwide. The present study aimed to investigate the pathogenesis of pneumonia and identify microRNA (miRNA) biomarkers as candidates for targeted therapy. RNA from the peripheral blood plasma of participants with pneumonia (severe, n=9; non-severe, n=9) and controls (n=9) was isolated and paired-end sequencing was performed on an Illumina HiSeq4000 system. Following the processing of raw reads, the sequences were aligned against the Genome Reference Consortium human genome assembly 38 reference genome using Bowtie2 software. Reads per kilobase of transcript per million mapped read values were obtained and the limma software package was used to identify differentially expressed miRNAs (DE-miRs). Then, DE-miR targets were predicted and subjected to enrichment analysis. In addition, a protein-protein interaction (PPI) network of the predicted targets was constructed. This analysis identified 11 key DE-miRs in pneumonia samples, including 6 upregulated miRNAs (including hsa-miR-34a and hsa-miR-455) and 5 downregulated miRNAs (including hsa-let-7f-1). All DE-miRs kept their upregulation/downregulation pattern in the control, non-severe pneumonia and severe pneumonia samples. Predicted target genes of DE-miRs in the subjects with non-severe pneumonia vs. the control and the subjects with severe pneumonia vs. the non-severe pneumonia group were markedly enriched in the adherens junction and Wnt signaling pathways. KALRN, Ras homolog family member A (RHOA), β-catenin (CTNNB1), RNA polymerase II subunit K (POLR2K) and amyloid precursor protein (APP) were determined to encode crucial proteins in the PPI network constructed. KALRN was predicted to be a target of hsa-mir-200b, while RHOA, CTNNB1, POLR2K and APP were predicted targets of hsa-let-7f-1. The results of the present study demonstrated that hsa-let-7f-1 may serve a role in the development of cancer and the Notch signaling pathway. Conversely, hsa-miR-455 may be an inhibitor of pneumonia pathogenesis. Furthermore, hsa-miR-200b might promote pneumonia via targeting KALRN.

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Section: Discussionmentioning

confidence: 91%

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

Huang¹,

Cong²,

Zhai³

et al. 2017

Experimental and Therapeutic Medicine

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“…ZEB1 is a member of the ZEB family of transcription factors, it contains two zinc finger clusters and a homeodomain (25). Growing evidence shows that ZEB1 plays an important role in cell proliferation, apoptosis, metastasis and angiogenesis (26)(27)(28)(29). EMT is a crucial step which cancer cells must pass before they can undergo metastasis and ZEB1 is one of the key inducers of epithelial-to-mesenchymal transition.…”

Section: Discussionmentioning

confidence: 99%

Oridonin inhibition and miR-200b-3p/ZEB1 axis in human pancreatic cancer

Gui

Luo

Yang

et al. 2016

International Journal of Oncology

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The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition (EMT) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array. The expression of miR‑200b-3p was verified by using real-time PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice and immunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer. We found that oridonin inhibited the proliferation of BxPC-3 and PANC-1 cells in a dose-dependent manner. miR-200b-3p was downregulated by oridonin in BxPC-3 and PANC-1 cells. ZEB1 was a target gene for miR-200b-3p. Oridonin or overexpression of miR‑200b-3p can inhibit the cell migration in BxPC-3 and PANC-1 cells. miR-200b-3p can inhibit the EMT and oridonin can inhibit the expression of ZEB1, N-cadherin and fibronectin but not increase the expression of E-cadherin, while the cell adhesion molecules ICAM-1 and VCAM-1 were decreased by oridonin in BxPC-3 and PANC-1 cells and the cytoskeleton was altered by oridonin in PANC-1 cells compared with the control. In summary, the results demonstrate that miR‑200b-3p was able to inhibit the EMT of human pancreatic cancer in vivo and in vitro by targeted ZEB1. In vitro, oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells, but not though type III EMT by miR-200-3p/ZEB1 axis, and may be related to type Ⅱ EMT, tumor microenvironment or altering the cytoskeleton. In vivo, oridonin inhibited the cancer migration in the nude mouse model though inhibiting EMT.

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“…Our previous study shows that miR-455 is a key regulator of brown adipose tissue that promotes differentiation of brown adipocytes by targeting Necdin, Runx1t1 and HIF1an [9]. Recent studies indicate that miR-455 could improve the progression of different cancers [10,11], while there is still lack of the research focused on the regulation of miR-455 on liver metabolism.…”

Section: Introductionmentioning

confidence: 99%

MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice

et al. 2020

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MiR-455 has been verified a key regulator of brown adipose tissue and adipose tissue-specific overexpression of miR-455 (ap2-miR-455) mice could combat high-fat-diet-induced obesity. This study is to verify overexpression of miR-455 could ameliorate the lipid accumulation and metabolism in the liver of db/db diabetic mice and explore the potential mechanisms. Diabetic mice (db/db) and control mice (db/ m) were randomly divided into four groups. After overexpression of miR-455 in the liver of db/db mice, the triglycerides level in both serum and liver decreased, the lipid deposit in liver was improved, the expression of fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase (ACCα) was also significantly down-regulated. TargetScan indicated that suppressor of cytokine signalling 3 (SOCS3) is predicated to target miR-455 and the protein of SOCS3 in the liver of db/db mice after intervention was significantly decreased. The dual luciferase reporter assay showed that SOCS3 was target gene of miR-455. In vitro, in Palmitate (PA)stimulated human normal liver (LO2) cells, transfected miR-455 mimic could significantly inhibit the expression of SOCS3, while transfected miR-455 inhibitor could up-regulate the expression of SOCS3. Transfecting LO2 cells with siRNA of SOCS3 could significantly down-regulate the protein expression of SREBP-1c and ACCα. Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene SOCS3.

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MicroRNA‐455 suppresses non‐small cell lung cancer through targeting ZEB1

Cited by 43 publications

References 32 publications

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

Oridonin inhibition and miR-200b-3p/ZEB1 axis in human pancreatic cancer

MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice

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