Overexpression of microRNA-125a-3p effectively inhibits the cell growth and invasion of lung cancer cells by regulating the mouse double minute 2 homolog/p53 signaling pathway

Li, Shenglei; Li, Xin; Zhao, Huasi; Gao, Ming; Wang, Feng; Li, Wencai

doi:10.3892/mmr.2015.4038

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…It has been shown that miR-125a-3p is downregulated and inhibits cell growth and invasion of LUAC [18][19][20][21]. In accordance, we found that miR-125a-3p expression was decreased in LUAC and associated with lymph node metastasis in patients with LUAC.…”

Section: Discussionsupporting

confidence: 85%

“…Some studies show that miR-125a-3p and miR-125a-5p, downregulated in NSCLC, possess the inverse effects on migration and invasion of lung cancer cells [18], and downregulation of miR-125a-3p is associated with tumorigenesis and poor prognosis in patients with NSCLC [19]. Moreover, miR-125a-3p represses lung cancer growth and invasion by regulating the mouse double minute 2 homolog/p53 signaling [20], and NSCLC proliferation and migration by targeting metastasis-associated gene 1 [21]. miR-125a-3p is also sponged by lncRNA MALAT1 to regulate FOXM1 expression in hepatocellular carcinoma [22], and sponged by circ-MAPK4 in gliomas, circ_0012919 in systemic lupus erythematous and circLMF1 in aortic smooth muscle cells [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

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Circular RNA Hsa_Circ_0002483 Promotes Growth and Invasion of Lung Adenocarcinoma by Sponging miR-125a-3p

Wei

Ding

Zhou

et al. 2021

Preprint

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Background: Increasing evidence indicates that the aberrant expression of circular RNAs (circRNAs) is involved in the pathogenesis and progression of lung adenocarcinoma (LUAC). However, the function and molecular mechanisms of hsa_circ_0002483 (circ_0002483) in LUAC remain unclear. Methods: The association between circ_0002483 expression and clinicopathological characteristics and prognosis in patients with LUAC was analyzed by fluorescence in situ hybridization. The functional experiments such as MTT, colony formation and Transwell assays and a subcutaneous tumor model were conducted to determine the role of circ_0002483 in LUAC cells. The specific binding between circ_0002483 and miR-125a-3p was validated by RNA immunoprecipitation, luciferase gene report and qRT-PCR assays. The effects of circ_0002483 on miR-125a-3p-mediated C-C motif chemokine ligand 4 (CCL4)-CCR5 axis were assessed by Western blot analysis.Results: We found that circ_0002483 was upregulated in LUAC tissue samples and associated with TNM stage and poor survival in patients with LUAC. Knockdown of circ_0002483 inhibited proliferation, colony formation and invasion of A549 and PC9 cells in vitro, whereas overexpression of circ_0002483 harbored the opposite effects. Furthermore, circ_0002483 sponged miR-125a-3p and negatively modulated its expression. CCL4 was identified as a direct target of miR-125a-3p. The rescue experiments showed that miR-125a-3p mimics reversed the tumor-promoting effects of circ_0002483 by targeting CCL4-CCR5 axis in A549 and PC9 cells. In addition, the in vivo experiment further validated that knockdown of circ_0002483 repressed tumor growth. Conclusions: Our findings demonstrated that circ_0002483 could act as a sponge of miR-125a-3p to upregulate CCL4-CCR5 axis, contributing to the tumorigenesis of LUAC, and represent a potential therapeutic target for LUAC.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Circular RNA Hsa_Circ_0002483 Promotes Growth and Invasion of Lung Adenocarcinoma by Sponging miR-125a-3p

Wei

Ding

Zhou

et al. 2021

Preprint

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“…The incidence of positive anti-p53 antibody in IPF, irrespective of the existence of lung cancer, was as high as that in lung cancer ( 27 ). These findings suggest that the p53-signaling pathway is associated with lung cancer ( 28 – 30 ) and with IPF ( 31 ). Thus, we hypothesized that p53 mutation downregulation may be associated with a high incidence of lung cancer in patients with IPF.…”

Section: Discussionmentioning

confidence: 81%

Low expression of long noncoding RNA CDKN2B-AS1 in patients with idiopathic pulmonary fibrosis predicts lung cancer by regulating the p53-signaling pathway

Hao

Liu

2018

Oncol Lett

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The present study aimed to investigate the expression of long non-coding RNA (lncRNA) cyclin dependent kinase inhibitor-2B-antisense RNA 1 CDKN2B-AS1 in patients with peripheral blood of idiopathic pulmonary fibrosis (IPF). A total of 24 patients with IPF and 24 healthy controls were included in the study, four patients with IPF and four healthy controls were selected randomly to extract RNA. There were no other diseases such as hypertension and diabetes in the two groups. RNA from peripheral blood was extracted by high-throughput sequencing and bioinformatics analysis was performed. Based on selected differentially expressed lncRNA and mRNA, gene ontology analysis was performed to screen out the tumor-associated mRNA. A total of 20 samples were chosen to avoid variance due to individual differences. A total of 20 patients with IPF, and 20 controls were further studied, RNA extracted from peripheral blood was used to verify the lncRNA and mRNA levels. A total of 440 lncRNAs were identified to be upregulated and 1,376 downregulated according to the screening results of differential expression. High-throughput sequencing and bioinformatics analysis demonstrated that the expression of CDKN2B-AS1 decreased significantly in patients with IPF compared with healthy controls. The adjacent gene mRNA of CDKN2B-AS1 was identified as CDKN2A, an important anti-oncogene, which is concentrated on the p53 signaling-pathway according to the Kyoto Encyclopedia of Genes and Genomes database. CDKN2A mRNA expression levels were lower in patients with IPF and higher in the control group. The expression of CDKN2B-AS1 and CDKN2A mRNA was significantly lower in IPF group compared with in the control group (P<0.05). The results suggest the expression of the CDKN2B-AS1 and adjacent gene, CDKN2A, are downregulated in the peripheral blood of patients with IPF, which activates the p53-signaling pathway to promote lung cancer formation.

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“…Similar results were showed in other studies in different kinds of cancers. Overexpression of hsa-miR-125a-3p significantly inhibited the proliferation and invasion of lung cancer cells, and also is readily accessible as a diagnostic biomarker for early-stage colon cancer (CRC) [29,30]. Exosomes secreted by human adipose-derived MSCs (adMSC-Exo) can transfer miR-125a to endothelial cells and promote angiogenesis through repressing the angiogenic inhibitor delta-like 4 (DLL4) by targeting its 3′ untranslated region [31].…”

Section: Discussionmentioning

confidence: 99%

Identification of cell cycle as the critical pathway modulated by exosome-derived microRNAs in gallbladder carcinoma

Zhang

et al. 2021

Med Oncol

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Gallbladder cancer (GBC), the most common malignancy in the biliary tract, is highly lethal malignant due to seldomly specific symptoms in the early stage of GBC. This study aimed to identify exosome-derived miRNAs mediated competing endogenous RNAs (ceRNA) participant in GBC tumorigenesis. A total of 159 differentially expressed miRNAs (DEMs) was identified as exosome-derived miRNAs, contains 34 upregulated exo-DEMs and 125 downregulated exo-DEMs based on the expression profiles in GBC clinical samples downloaded from the Gene Expression Omnibus database with the R package. Among them, 2 up-regulated exo-DEMs, hsa-miR-125a-3p and hsa-miR-4647, and 5 down-regulated exo-DEMs, including hsa-miR-29c-5p, hsa-miR-145a-5p, hsa-miR-192-5p, hsa-miR-194-5p, and hsa-miR-338-3p, were associated with the survival of GBC patients. Results of the gene set enrichment analysis showed that the cell cycle-related pathways were activated in GBC tumor tissues, mainly including cell cycle, M phase, and cell cycle checkpoints. Furthermore, the dysregulated ceRNA network was constructed based on the lncRNA-miRNA-mRNA interactions using miRDB, TargetScan, miRTarBase, miRcode, and starBase v2.0., consisting of 27 lncRNAs, 6 prognostic exo-DEMs, and 176 mRNAs. Together with prognostic exo-DEMs, the STEAP3-AS1/hsa-miR-192-5p/MAD2L1 axis was identified, suggesting lncRNA STEAP3-AS1, might as a sponge of exosome-derived hsa-miR-192-5p, modulates cell cycle progression via affecting MAD2L1 expression in GBC tumorigenesis. In addition, the biological functions of genes in the ceRNA network were also annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Our study promotes exploration of the molecular mechanisms associated with tumorigenesis and provide potential targets for GBC diagnosis and treatment.

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Overexpression of microRNA-125a-3p effectively inhibits the cell growth and invasion of lung cancer cells by regulating the mouse double minute 2 homolog/p53 signaling pathway

Cited by 14 publications

References 28 publications

Circular RNA Hsa_Circ_0002483 Promotes Growth and Invasion of Lung Adenocarcinoma by Sponging miR-125a-3p

Circular RNA Hsa_Circ_0002483 Promotes Growth and Invasion of Lung Adenocarcinoma by Sponging miR-125a-3p

Low expression of long noncoding RNA CDKN2B-AS1 in patients with idiopathic pulmonary fibrosis predicts lung cancer by regulating the p53-signaling pathway

Identification of cell cycle as the critical pathway modulated by exosome-derived microRNAs in gallbladder carcinoma

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