MicroRNA-103a-3p Promotes Cell Proliferation and Invasion in Non-Small-Cell Lung Cancer Cells through Akt Pathway by Targeting PTEN

Li, Haixun; Huhe, Muren; Lou, Jiaxin

doi:10.1155/2021/7590976

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…Several direct targets have been identified, including AKAP12 in hepatocellular carcinoma, PTEN in non-small-cell lung cancer and D52 in prostate cancer, have been reported to be targets of miR-103a-3p [ 38 , 41 , 44 ]. In our current study, FBXW7 was validated as a direct and functional target of miR-103a-3p in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

et al. 2022

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MicroRNAs (miRNAs) have been reported to be involved in the initiation and progression of human tumors including cervical cancer (CC). However, the mechanisms underlying of their actions in CC remain to be fully elucidated. Herein, the differentially expressed miRNAs that were screened based on GSE55940 microarray data retrieved from Gene Expression Omnibus (GEO), and miR-103a-3p was significantly upregulated in CC tissues which was selected as the target miRNA for further research. We also found that high expression of miR-103a-3p was closely associated with histological grades, FIGO stage and distant metastasis as well as reflected poor overall survival. Moreover, miR-103a-3p inhibition decreased the growth capacity of SiHa and HeLa cells by inducing cell apoptosis. And F-box and WD repeat-domain containing protein 7 (FBXW7), a well-known tumor suppressor in many cancer types, was identified as a direct target of miR-103a-3p. It was further found that FBXW7 was significantly downregulated in CC tissues, and it was inversely correlated with miR-103a-3p expression levels. Further investigation demonstrated that FBXW7 upregulation could simulate the roles of miR-103a-3p knockdown in cell viability and apoptosis. Moreover, FBXW7 knockdown efficiently abrogated the influences of CC cells proliferation caused by miR-103a-3p inhibition. Notably, miR-103a-3p could block FBXW7 mediated the downstream transcription factor pathways. Taken together, these findings suggest that miR-103a-3p functions as an oncogene in CC by targeting FBXW7.

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Section: Discussionmentioning

confidence: 99%

The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

et al. 2022

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“…A recent study also reported that miR-103a-3p was upregulated in EVs during ZIKV infection ( Tabari et al, 2020 ). MiR-103a-3p has multiple functions involved in the regulation of inflammation, immune response, and development of a variety of cancers ( Geng et al, 2014 ; Hu et al, 2018 ; Lu et al, 2019 ; Li et al, 2020 , 2021 ). However, to date, the effect of miR-103a-3p on the regulation of pathogen infection has not been reported.…”

Section: Discussionmentioning

confidence: 99%

MiR-103a-3p Promotes Zika Virus Replication by Targeting OTU Deubiquitinase 4 to Activate p38 Mitogen-Activated Protein Kinase Signaling Pathway

et al. 2022

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BackgroundMicroRNAs (miRNAs) play critical roles in regulating virus infection and replication. However, the mechanism by which miRNA regulates Zika virus (ZIKV) replication remains elusive. We aim to explore how the differentially expressed miR-103a-3p regulates ZIKV replication and to clarify the underlying molecular mechanism.MethodsSmall RNA sequencing (RNA-Seq) was performed to identify differentially expressed miRNAs in A549 cells with or without ZIKV infection and some of the dysregulated miRNAs were validated by quantitative real time PCR (qRT-PCR). The effect of miR-103a-3p on ZIKV replication was examined by transfecting miR-103a-3p mimic or negative control (NC) into A549 cells with or without p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and expression levels of ZIKV NS5 mRNA and NS1 protein were detected by qRT-PCR and Western blot, respectively. The potential target genes for miR-103a-3p were predicted by four algorithms and further validated by mutation analysis through luciferase reporter assay. The predicated target gene OTU deubiquitinase (DUB) 4 (OTUD4) was over-expressed by plasmid transfection or silenced by siRNA transfection into cells prior to ZIKV infection. Activation status of p38 MAPK signaling pathway was revealed by looking at the phosphorylation levels of p38 (p-p38) and HSP27 (p-HSP27) by Western blot.ResultsThirty-five differentially expressed miRNAs in ZIKV-infected A549 cells were identified by RNA-Seq analysis. Five upregulated and five downregulated miRNAs were further validated by qRT-PCR. One of the validated upregulated miRNAs, miR-103a-3p significantly stimulated ZIKV replication both at mRNA (NS5) and protein (NS1) levels. We found p38 MAPK signaling was activated following ZIKV infection, as demonstrated by the increased expression of the phosphorylation of p38 MAPK and HSP27. Blocking p38 MAPK signaling pathway using SB203580 inhibited ZIKV replication and attenuated the stimulating effect of miR-103a-3p on ZIKV replication. We further identified OTUD4 as a direct target gene of miR-103a-3p. MiR-103a-3p over-expression or OTUD4 silencing activated p38 MAPK signaling and enhanced ZIKV replication. In contrast, OTUD4 over-expression inhibited p38 MAPK activation and decreased ZIKV replication. In addition, OTUD4 over-expression attenuated the stimulating effect of miR-103a-3p on ZIKV replication and activation of p38 MAPK signaling.ConclusionZika virus infection induced the expression of miR-103a-3p, which subsequently activated p38 MAPK signaling pathway by targeting OTUD4 to facilitate ZIKV replication.

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“…Cell Proliferation Assay. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, as previously described [16]. Cells were plated in 96-well plates at a density of 1 × 10 3 cells/well.…”

Section: 2mentioning

confidence: 99%

“…Transwell chambers (Millipore, Billerica, MA, USA) containing Matrigel were used to determine the invasive ability of cells [16]. A total of 1 × 10 5 cells in RPMI-1640 serum-free growth medium (Gibco, USA) were seeded in the upper wells, whereas the lower wells were filled with the same medium containing 10% serum.…”

Section: Transwell Invasion Assaymentioning

confidence: 99%

Long Noncoding RNA LINC01554 Inhibits the Progression of NSCLC Progression by Functioning as a ceRNA for miR-1267 and Regulating ING3/Akt/mTOR Pathway

Wang

Yang

Zhang

et al. 2022

BioMed Research International

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Objectives. This study focused on the biological functions and mechanisms of action of LINC01554 in nonsmall cell lung cancer (NSCLC). Methods. The expression and prognostic values of LINC01554 in NSCLC were evaluated using The Cancer Genome Atlas datasets. MTT, colony formation, wound healing, transwell, and in vivo assays were performed to investigate the role of LINC01554 in NSCLC. The related protein expression levels were measured via western blotting. Bioinformatic analysis was conducted to predict targeted genes. The relationship between LINC01554, microRNA- (miR-) 1267, miR-1267, and inhibitor of growth family member 3 (ING3) was analysed via a dual-luciferase reporter assay. Results. LINC01554 expression was downregulated in NSCLC and associated with NSCLC prognosis. LINC01554 overexpression suppressed NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Bioinformatic and dual-luciferase reporter assays demonstrated that LINC01554 expression directly targeted miR-1267 expression, which in turn directly acted on ING3. An miR-1267 mimic significantly reduced ING3 expression, whereas an miR-1267 inhibitor observably elevated its expression. LINC01554 overexpression increased ING3 expression, whereas this effect was counteracted by the miR-1267 mimic. LINC01554 overexpression also significantly suppressed the expression of phosphorylated protein kinase B (Akt) and phosphorylated mammalian target of rapamycin (mTOR) expression; this effect was abrogated by the miR-1267 mimic. Mechanistically, LINC01554 overexpression repressed the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells through the regulation of the miR-1267/ING3 axis via regulation of the Akt/mTOR signalling pathway. Conclusions. We provide the first evidence of the involvement of the LINC01554/miR-1267 axis in NSCLC proliferation and metastasis through the ING3Akt/mTOR pathway. Thus, LINC01554 may serve as a novel therapeutic target for NSCLC.

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MicroRNA-103a-3p Promotes Cell Proliferation and Invasion in Non-Small-Cell Lung Cancer Cells through Akt Pathway by Targeting PTEN

Cited by 11 publications

References 29 publications

The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

MiR-103a-3p Promotes Zika Virus Replication by Targeting OTU Deubiquitinase 4 to Activate p38 Mitogen-Activated Protein Kinase Signaling Pathway

Long Noncoding RNA LINC01554 Inhibits the Progression of NSCLC Progression by Functioning as a ceRNA for miR-1267 and Regulating ING3/Akt/mTOR Pathway

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