MiR-139-5p negatively regulates PMP22 to repress cell proliferation by targeting the NF-κB signaling pathway in gastric cancer

Hou, Jingjing; Zhuo, Huiqin; Chen, Xin; Cheng, Jia; Zheng, Wei; Zhong, Min; Cai, Jun

doi:10.7150/ijbs.40338

Cited by 26 publications

(17 citation statements)

References 44 publications

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“…Combined with bioinformatics analysis (TargetScan, miRDB and miRWalk), we discovered that three candidate miRNAs potentially bound with HOXA13 (Figure 7A). Among these miRNAs, only miR-139-5p was involved in the progression of gastric cancer according to previous reports (24)(25)(26), which was further verified downregulated in GC cells compared to GES-1 and negatively associated with the expression of HOXA13 in GC tissues in our 7B, C). Therefore, miR-139-5p was selected as a putative candidate for further validation.…”

Section: Hoxa13 Is Directly Targeted By Mir-139-5psupporting

confidence: 82%

HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4

Chen

Qin

et al. 2021

Front. Oncol.

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PurposeChemoresistance remains a major challenge in the therapy of gastric cancer (GC). The homeobox (HOX) gene family has gained attention in carcinogenesis and chemoresistance. Here, this study aimed to explore the mechanism of HOXA13 in GC chemoresistance.MethodsQuantitative real-time PCR (qRT-PCR) and Western blot were used to evaluate the expression of HOXA13 in GC tissues. The Kaplan–Meier plotter database was mined for prognosis analysis of GC patients with different HOXA13 expression receiving 5-Fluorouracil (5-FU) therapy. The effects of HOXA13 on sensitivity of GC cells to 5-FU were investigated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2’-deoxyuridine (EdU) incorporation, flow cytometry and experiment in vivo. RNA-Sequencing analysis was performed to explore the underlying mechanism of HOXA13-mediated 5-FU resistance in GC. Chromatin immunoprecipitation (ChIP) and rescue experiments were applied to determine the relationship between HOXA13 and ABCC4. Luciferase reporter assay was performed to assess interaction of miR-139-5p and HOXA13.ResultsHOXA13 was upregulated in GC and its high expression was associated with poor prognosis of GC patients with 5-FU treatment. Overexpression of HOXA13 impaired the inhibitory effects of 5-FU on GC cells proliferation in vitro and vivo, and knockdown of HOXA13 exacerbated 5-FU-induced GC cells apoptosis. Mechanistically, HOXA13, directly targeted by miR-139-5p in GC, might upregulate ABCC4 expression, thereby accentuating 5-FU resistance of GC cells.ConclusionOur study suggests that HOXA13 attenuates 5-FU sensitivity of GC possibly by upregulating ABCC4. Thus, targeting HOXA13 would provide a novel prospective into the potential therapeutic strategy for reversing chemoresistance.

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Section: Hoxa13 Is Directly Targeted By Mir-139-5psupporting

confidence: 82%

HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4

Chen

Qin

et al. 2021

Front. Oncol.

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“…In the current investigation, we employed microarray analysis to screen out the top 10 differentially expressed miRNAs in exosome‐treated trophoblasts, among which miR‐139‐5p was revealed to be the most significantly expressed one (Fold change ≈ 9). miR‐139‐5p has been indicated to mediate the expression of peripheral myelin protein 22 to block cell growth and proliferation by governing the nuclear factor‐κB signaling pathway in gastric cancer 28 . Interestingly, it has been proposed that mice treated with exosomes extracted from patients with depression presented depressive‐like behaviors, which was connected with miR‐139‐5p‐controlled neurogenesis 29 .…”

Section: Discussionmentioning

confidence: 99%

“…miR-139-5p has been indicated to mediate the expression of peripheral myelin protein 22 to block cell growth and proliferation by governing the nuclear factor-κB signaling pathway in gastric cancer. 28 Interestingly, it has been proposed that mice treated with exosomes extracted from patients with depression presented depressive-like behaviors, which was connected with miR-139-5p-controlled neurogenesis. 29 Extracellular miRNAs circulating at the second trimester in parental blood are linked with fetal development, and miR-139-5p was associated with weight-for-gestational age zscore.…”

Section: Ameliorative Effect Of Exosomes On Pe Ratsmentioning

confidence: 99%

Exosomal microRNA‐139‐5p from mesenchymal stem cells accelerates trophoblast cell invasion and migration by motivation of the ERK/MMP‐2 pathway via downregulation of protein tyrosine phosphatase

Liu

Wang²,

Zhang³

et al. 2020

J of Obstet and Gynaecol

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Aim: Exosomes present essential roles for intercellular interaction via extracellular pathways during systemic dysfunctions, including preeclampsia (PE). Here, we assessed the specific mechanism of mesenchymal stem cells (MSC)-originated exosomes in PE. Methods: The effects of exosomes on trophoblasts were studied by EdU, wound healing, Transwell and TUNEL assays. By microarray analysis, we found that exosomes enhanced the microRNA-139-5p (miR-139-5p) in trophoblasts, and confirmed the target gene of miR-139-5p by bioinformatics prediction and dualluciferase reporter gene assay. At the same time, ERK/MMP-2 pathway-related biomolecules were assessed through Western blot analysis. The pathway inhibitor was used for rescue experiments. Finally, the effect of exosomes on the pathology of PE rats was verified by in vivo experiments. Results: The exosomes originated from hucMSC fostered the trophoblast cell migration, invasion and proliferation and obstructed apoptosis. Moreover, miR-139-5p could be transmitted to trophoblasts through hucMSC-secreted exosomes. miR-139-5p targeted protein tyrosine phosphatase (PTEN), which regulated the ERK/MMP-2 pathway. Inhibition of the ERK/MMP-2 pathway significantly reduced the promoting effect of exosomes on trophoblasts. Treatment with exosomes significantly lowered blood pressure values and reduced 24-h proteinuria in PE rats. Conclusion: hucMSC-originated exosomes overexpressing miR-139-5p activated the ERK/MMP-2 pathway via PTEN downregulation, thus accelerating trophoblast cell invasion and migration, and blocking apoptosis. These results demonstrated that hucMSC-derived exosomes overexpressing miR-139-5p might be an innovative direction for therapeutic approaches against PE.

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“…Upregulation of miR-139-5p not only can reduce the oxidative stress and apoptosis of rat hippocampal neurons induced by epileptiform discharges by regulating the Notch pathway (27), but also can protect diabetic mice from liver tissue damage and oxidative stress by inhibiting the Notch signaling pathway(28). MiR-139-5p not only can negatively regulate PMP22 by targeting the NF-κB signaling pathway to inhibit gastric cancer cell proliferation (29), but also can regulate the proliferation, apoptosis and cell cycle of uterine leiomyoma cells by targeting TPD52 (30). However, the correlation between miR-520d-5p and miR-139-5p and RA has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Potential Biological Molecules and Immune Cell for Rheumatoid Arthritis Synovial Lesions

Yang

et al. 2021

Preprint

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Objective: To study the potential biomarkers and related pathways in rheumatoid arthritis (RA) synovial lesions, as well as immune cell, to provide theoretical basis and research directions for the mechanism and treatment of RA. Methods: Download the RA synovial tissue microarray data set (GSE77298, GSE55457 and GSE55235) from Gene Expression Omnibus (GEO), The“limma” package of R to identify differentially expressed genes (DEGs), DAVIA Perform GO (Gene Ontology, gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes, Kyoto Gene Encyclopedia) enrichment analysis. STRING (Search Tool for the Retrieval of Interacting Genes) constructs a Protein Protein Interaction Network (PPI), R screens Hub genes, and mines targeted miRNAs of Hub genes based on multiple databases. In R,the immune cell of RA synovial tissue samples are obtained through the three packages of "e1071", "parallel" and "preprocessCore" with "CIBERSORT" software. Results: Ten Hub genes (KIAA0101, FOXM1, EGFR, CDC20, BUB1B, TYMS, TOP2A, RRM2, JUN and CCNA2) and 2 key miRNAs (miR-520d-5p and miR) related to RA synovial lesions were finally identified -139-5p), significantly enriched in epithelial cell signaling, ECM-receptor interaction, estrogen signaling pathway, cell cycle, ErbB signaling pathway and GnRH signaling pathway in Helicobacter pylori infection. Immune cell analysis found that resting dendritic cells, B cells memory, dendritic cells activated, plasma cells, macrophages M1, mast cells resting and T cells regulatory have high expression in RA, while neutrophils, B cells naive and natural killer cells activated have low expression in RA. Conclusion:The Hub genes, key miRNAs, related pathways, and immune cell obtained in this study provide a certain basis for the etiology and treatment of RA synovial lesions.

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MiR-139-5p negatively regulates PMP22 to repress cell proliferation by targeting the NF-κB signaling pathway in gastric cancer

Cited by 26 publications

References 44 publications

HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4

HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4

Exosomal microRNA‐139‐5p from mesenchymal stem cells accelerates trophoblast cell invasion and migration by motivation of the ERK/MMP‐2 pathway via downregulation of protein tyrosine phosphatase

Potential Biological Molecules and Immune Cell for Rheumatoid Arthritis Synovial Lesions

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