MicroRNA-21 promotes TGF-β1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression

Li, Chang; Song, Lei; Zhang, Zhuo; Bai, Xiaoxue; Cui, Min; Ma, Lu‐Fang

doi:10.18632/oncotarget.11888

Cited by 58 publications

(50 citation statements)

References 29 publications

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“…miR-21 was overexpressed in human keloid fibroblasts induced by TGF-β1 [41]. Besides, miR-21 could promote TGF-β1-induced EMT in gastric cancer cells [42] and promotes breast cancer progression and chemoresistance through TGF-β1 stimulation [43]. Since an in vivo model system of nasal polyps has not been established, the results of our tissue experiments showed the significantly increased expression of miR-21 in CRSwNP.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Recently, miR-21 has been ascribed a crucial role in the regulation of cellular activity during physiological and pathological processes [31]. miR‑21 is widely expressed and has been found to be increased in organs and tissues which have suffered fibrogenesis or remodeling, including the heart [32], kidney [33], lung [34], asthmatic airways [35, 36], liver [37, 38], skin [39-41], and tumor tissue [42, 43]. Studies revealed that enhanced miR-21 expression is involved in the progression of lung fibrosis, and TGF-β1 plays an important role in mediating increased miR-21 expression [34, 44].…”

Section: Introductionmentioning

confidence: 99%

“…However, there are no studies investigating the expression changes in miR-21 and the relationship between miR-21 and TGF-β1 in EMT of CRSwNP in particular. Although TGF-β/Smad signaling is regarded as the main pathway in EMT, TGF-β also activates a Smad-independent signaling pathway, with the direct involvement of TGF-β-activated kinase [42, 43, 45, 46]. Since past researches confirm that PTEN is an miR-21-directed target gene, we hypothesized that miR-21 mediated TGF-β1-induced EMT through the PTEN/Akt pathway in PHNECs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Zhu

et al. 2019

Int Arch Allergy Immunol

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Objectives: To characterize the epithelial-mesenchymal transition (EMT) in chronic rhinosinusitis with nasal polyps (CRSwNP) and to investigate the mechanism by which microRNA-21 (miR-21) regulates EMT in CRSwNP. Method: (1) Tissue experiments: Mucosa tissues were collected from 13 patients with CRSwNP and 12 patients with CRS without nasal polyps (CRSsNP), as well as 11 patients without CRS (controls). Protein localization and quantification were achieved by immunofluorescence staining and Western blotting, involving the epithelial marker protein E-cadherin and the mesenchymal marker proteins α-smooth muscle actin (α-SMA), fibronectin, and vimentin. Quantitative RT-PCR was used to detect the relative expression levels of miR-21 and TGF-β1 mRNAs. (2) Cellular experiments: Primary human nasal epithelial cells (PHNECs) treated with TGF-β1, or TGF-β1 with miR-21 inhibitor, or miR-21 mimics alone were observed for morphology changes under a phase-contrast microscope. The expression levels of epithelial/mesenchymal marker proteins were determined as aforementioned. PTEN and phosphorylated Akt were detected by Western blotting. Results: (1) Tissue experiments: Compared with the CRSsNP and control groups, the expression of E-cadherin was downregulated in the CRSwNP group, whereas the expression of TGF-β1, α-SMA, fibronectin, and vimentin was upregulated. The expression levels of miR-21 and TGF-β1 mRNAs in CRSwNP were significantly higher than those in CRSsNP and controls. (2) Cellular experiments: TGF-β1 induced EMT-like transformation in PHNECs, featured by changes in cell morphology and upregulation of mesenchymal proteins and miR-21. The miR-21 inhibitor, as well as the Akt-specific inhibitor, suppressed TGF-β1-induced EMT. Mechanically, downregulation of miR-21 resulted in increased PTEN and decreased Akt phosphorylation. Furthermore, overexpression of miR-21 had the opposite effects. Conclusions: Our findings suggest that the TGF-β1-miR-21-PTEN-Akt axis may contribute to the pathogenesis of CRSwNP. miR-21 might be a reliable target for treating nasal polyp genesis through EMT suppression. Moreover, miR-21 inhibitors could be a novel class of antipolyp drug that modulates PTEN expression and Akt activation. In addition, further investigation regarding the reason underlying miR-21 overexpression in CRSwNP could provide a molecular target for novel treatment strategies for nasal polyposis.

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Section: Discussion/conclusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Zhu

et al. 2019

Int Arch Allergy Immunol

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“…Numerous studies have demonstrated that microRNAs (miRNAs) are involved in the process of epithelial-mesenchymal transition (EMT) in various types of cancer (3)(4)(5)(6), and various studies have revealed that the EMT may be associated with the drug resistance of cancer cells (7)(8)(9)(10). Furthermore, by comparing the miRNA expression profiles between breast cancer cell lines in our previous study, we determined that the expression of miR-93 was increased markedly in drug-resistant MCF-7/AdrVp cells compared with the parental MCF-7 cell line (11).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies on breast cancer have demonstrated that PTEN is involved in EMT (5,12) and in the drug resistance of cancer cells (6,13). Although a few studies have shown that miR-93 may functionally interact with PTEN, this has only been reported in cardiomyocyte apoptosis, osteosarcoma, ovarian cancer, glioma, hepatocellular carcinoma and prostate cancer (14)(15)(16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

Chu

Xia

et al. 2017

Oncology Reports

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Abstract. It is not well established whether miR-93 is involved in drug resistance and epithelial-mesenchymal transition (EMT) in breast cancer, and its underlying mechanism remains uncertain. In the present study, the expression differences of miR-93 between paired breast cancer tissues confirmed it is involved in the progression of breast cancer. Such a difference was also observed in doxorubicin-resistant and -sensitive cells. Overexpressed miR-93 in sensitive cells revealed increases in cellular proliferation and the expression levels of drug-resistant-related genes, and a decrease in sensitivity to doxorubicin. This demonstrated the relationship between miR-93 and breast cancer drug resistance. Simultaneously, EMT was confirmed in miR-93 overexpressing sensitive cells. This indicated the triadic relationship among miR-93, EMT and drug resistance in breast cancer. We applied the Dual-luciferase Reporter assay to expose the direct interaction between miR-93 and PTEN, which suggested that miR-93 contributes to inducing EMT and drug resistance of breast cancer cells by targeting PTEN.

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MiR‐21 improves invasion and migration of drug‐resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1

Che

et al. 2018

Cancer Medicine

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This study was aimed at the investigation of the effects of miR‐21 on drug resistance, invasion, migration, and epithelial–mesenchymal transition (EMT) of lung adenocarcinoma cells and the related molecular mechanisms. Cell viability of A549 cell line was measured by MTT assay. Wound healing assay and transwell assay were, respectively, employed to examine cell migration and invasion abilities. The cells were transfected with miR‐21 mimic or inhibitor using Lipofectamine 3000. The target relationship between miR‐21 and HBP1 was confirmed by luciferase reporter gene assay. Western blot and qRT‐PCR were used to examine the expression of HBP1 and EMT‐related molecules. Compared with A549 cells, drug resistance of A549/PTX cells and A549/DDP cells were obviously stronger. A549/PTX cells and A549/DDP cells had stronger ability of migration and invasion compared with parental A549 cells. Meanwhile, EMT of A549/PTX and A549/DDP was significantly higher than that of A549 cells. MiR‐21 promoted migration, invasion, and EMT of human lung adenocarcinoma cancer cells. Our experiment also verified the target relationship between miR‐21 and HBP1. MiR‐21 may affect migration and invasion ability of drug‐resistant lung adenocarcinoma cells by targeting HBP1, therefore modulating EMT.

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MicroRNA-21 promotes TGF-β1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression

Cited by 58 publications

References 29 publications

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

MiR‐21 improves invasion and migration of drug‐resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1

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