miR‑29a‑3p regulates the epithelial‑mesenchymal transition via the SPARC/ERK signaling pathway in human bronchial epithelial cells

Zhang, Xiaobo; Xie, Jun; Sun, Hongmei; Nong, Guangmin

doi:10.3892/ijmm.2021.5004

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…SPARC expression was increased in mouse models with an epithelial-mesenchymal transition phenotype and SPARC expression had an effect on lung function in both human bronchial epithelial cells and mouse models (53,54). The SPARC fragment binding with the present ligand protein inhibited tumor cell adhesion, while promoting spreading and stimulating tumor cell migration and invasion, suggesting an important effect of SPARC expression on lung cancer development and progression (55)(56)(57). Univariate analysis suggested that TNM stage, lymph node metastasis, distant metastasis and smoking history were associated with poor prognosis in patients with NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Shi

Zhang

et al. 2022

Oncol Lett

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The aim of the present study was to elucidate the significance of secreted protein acidic and cysteine rich (SPARC) expression in non-small cell lung cancer (NSCLC) in terms of clinicopathology, immune-cell infiltration and survival prognosis. A meta-analysis and bioinformatics analysis were performed using studies retrieved with PubMed, Web of Science, Wanfang Data and the Chinese National Knowledge Infrastructure databases. The meta-analysis suggested that, compared with normal tissues, SPARC expression was elevated in NSCLC tissues. The expression of SPARC was not significantly associated with TNM stage and lymph-node metastasis, and was positively associated with patient gender. Regarding the differential expression of SPARC and the relationship between expression levels and survival, the Oncomine database was consulted and Kaplan-Meier curves were drawn. It was indicated that SPARC mRNA expression levels were higher in NSCLC tissues than in normal tissues. Low expression of SPARC mRNA was negatively associated with overall survival, first progression survival and post-progression survival of patients. Further exploration of the relationship between SPARC expression and survival by univariate analysis indicated that TNM stage, lymph node metastasis, distant metastasis and depth of infiltration of lung cancer were negatively associated with patient prognosis. Cox multifactorial analysis suggested that SPARC expression levels and TNM stage were risk factors significantly affecting the prognosis of patients with NSCLC. Analysis with the GEPIA and UALCAN databases further indicated that the mRNA expression level of SPARC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was higher than that in normal lung tissue, and the SPARC expression levels were affected by factors such as the TNM stage of lung cancer.A lower the level of SPARC mRNA expression was associated with a better relative survival prognosis of patients. In the Human Protein Atlas database, the expression level of SPARC protein was higher in LUAD and LUSC than in normal lung tissue. In the Timer database, the expression level of SPARC was closely linked to immune cells related to the occurrence of lung cancer, and the degree of immune-cell infiltration and SPARC protein expression were closely related to the prognosis of patients with lung cancer. Immune cells were indicated to exhibit significant inhibition of DNA proliferation mutation mechanisms in lung cancer (P<0.05). In summary, SPARC expression may be used as a valuable indicator of prognosis in patients with NSCLC, which may provide new approaches for preventative treatment.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Shi

Zhang

et al. 2022

Oncol Lett

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“…Epithelium damage and deficiency have been reported to result in EMT, which is considered to be intricately involved in AR and is the main cause of fixed airflow limitations that occur during asthma attacks (26,71). In contrast, inhibition of the EMT process can alleviate AR in asthma.…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma

Peng,

Sun,

Jiang

et al. 2023

Front. Immunol.

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BackgroundTGF-β1 can induce epithelial-mesenchymal transition (EMT) in primary airway epithelial cells (AECs). Semaphorin7A (Sema7a) plays a crucial role in regulating immune responses and initiating and maintaining transforming growth factor β1 TGF-β1-induced fibrosis.ObjectiveTo determine the expression of Sema7a, in serum isolated from asthmatics and non-asthmatics, the role of Sema7a in TGF-β1 induced proliferation, migration and airway EMT in human bronchial epithelial cells (HBECs) in vitro.MethodsThe concentrations of Sema7a in serum of asthmatic patients was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Sema7a and integrin-β1 were examined using conventional western blotting and real-time quantitative PCR (RT-PCR). Interaction between the Sema7a and Integrin-β1 was detected using the Integrin-β1 blocking antibody (GLPG0187). The changes in EMT indicators were performed by western blotting and immunofluorescence, as well as the expression levels of phosphorylated Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) were analyzed by western blot and their mRNA expression was determined by RT-PCR.ResultsWe described the first differentially expressed protein of sema7a, in patients with diagnosed bronchial asthma were significantly higher than those of healthy persons (P<0.05). Western blotting and RT-PCR showed that Sema7a and Integrin-β1 expression were significantly increased in lung tissue from the ovalbumin (OVA)-induced asthma model. GLPG0187 inhibited TGF-β1-mediated HBECs EMT, proliferation and migration, which was associated with Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) phosphorylation.ConclusionSema7a may play an important role in asthma airway remodeling by inducing EMT. Therefore, new therapeutic approaches for the treatment of chronic asthma, could be aided by the development of agents that target the Sema7a.

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“…As a member of the MAPK family, ERK1/2 transduces extracellular signals to intracellular signaling cascades, thereby regulating cell behaviors, including cell proliferation and differentiation [ 48 ]. Numerous studies have shown that the ERK/MAPK signaling pathway has crucial roles in tumorigenesis and metastasis [ 49 , 50 ]. HOXC6 has been shown to facilitate the proliferation and migration of glioblastoma cells by activating the ERK/MAPK signaling pathway [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development

Wang

Zhong

et al. 2022

Burns &Amp; Trauma

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Background A keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However, the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts, providing new ideas for the prevention and treatment of keloids. Methods We utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 (HOXC6) emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction, western blot (WB) and immunohistochemistry. Subsequently, the effects of downregulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8, flow cytometry, transwell migration and WB assays. Meanwhile, we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments. Results HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of HOXC6 inhibited proliferation, migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with HOXC6 in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of HOXC6 in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates HOXC6, contributing to KFs proliferation, migration, apoptosis inhibition and collagen accumulation through the ERK signaling pathway. Conclusions Our findings first revealed that HOXC6 acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation, migration and ECM production by KFs, contributing to the progression of keloids. Taken together, HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.

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miR‑29a‑3p regulates the epithelial‑mesenchymal transition via the SPARC/ERK signaling pathway in human bronchial epithelial cells

Cited by 4 publications

References 32 publications

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma

Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development

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