miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4

Du, Feiya; Yu, Liguo; Wu, Ying; Wang, Shuqian; Yao, Jia; Zheng, Xiaoxiao; Xie, Shangzhi; Zhang, Shufeng; Lu, Xuemei; Liu, Yu; Chen, Wei

doi:10.1038/s41419-019-2164-2

Cited by 57 publications

(37 citation statements)

References 45 publications

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“…Western blot analysis was performed as described previously [35][36][37] . Anti-PIK3R5, N-cadherin, E-cadherin, Vimentin, MMP2, Beclin1, p62, ATG5, LC3-II, Bax, Bcl2, cleaved caspase-3, and GAPDH were purchased from Abcam (Cambridge, UK), and anti-p-AKT, AKT, p-mTOR, and mTOR were obtained from Cell Signaling Technology.…”

Section: Western Blotmentioning

confidence: 99%

miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells

et al. 2020

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Osteosarcoma (OS) is a malignant bone tumor which occurs mainly in adolescents with frequent pulmonary metastasis and a high mortality rate. Accumulating evidence has indicated that microRNAs (miRNAs) play a vital role in various tumors by modulating target genes as well as signal pathways, and aberrant expression of miRNAs may contribute to OS progression. This study aimed to determine the association between miR-210-5p expression and OS progression and to investigate its potential underlying mechanism. Using reverse transcription-polymerase chain reaction (RT-PCR), miR-210-5p was found to be upregulated in clinical OS specimens and cell lines. Further functional analysis demonstrated that miR-210-5p promoted epithelial-mesenchymal transition (EMT) and induced oncogenic autophagy. Luciferase reporter assay, RNA-ChIP, and western blot analysis confirmed that PIK3R5, an essential regulator in the AKT/mTOR signaling pathway, is a target downstream gene of miR-210-5p. Overexpression or knockdown of PIK3R5 reversed the functional role of overexpression or knockdown of miR-210-5p, respectively. Silencing autophagyrelated gene 5 (ATG5) abolished the functional effects of miR-210-5p upregulation or PIK3R5 knockdown in OS cells. In vivo, miR-210-5p overexpression promoted OS tumor growth and pulmonary metastasis. Taken together, our results demonstrated that miR-210-5p promoted EMT and oncogenic autophagy by suppressing the expression of PIK3R5 and regulating the AKT/mTOR signaling pathway. Therefore, inhibition of miR-210-5p may represent a promising treatment for OS.

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Section: Western Blotmentioning

confidence: 99%

miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells

et al. 2020

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“…Then we looked back ΔNp63α-induced EEC-transcriptomes, and found that DUSP4 was one of the most upregulated gene, and it was known to be an important EMT promoting molecule 27,28 . To verify the promoting effect of ΔNp63α on the expression of DUSP4, we measured the protein level of DUSP4 in EECs infected with Ad-ΔNp63α, and found that DUSP4 protein was elevated by 1.5-fold (Fig.…”

Section: δNp63α Induces Dusp4 Downregulated Gsk3β Expression In Eecsmentioning

confidence: 99%

ΔNp63α-induced DUSP4/GSK3β/SNAI1 pathway in epithelial cells drives endometrial fibrosis

Zhao

Cao

et al. 2020

Cell Death Dis

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Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine adhesions (IUAs). Since ΔNp63α is profoundly involved in maintaining the epithelial homeostasis, we hereby focused on its roles in regulating the function and phenotype of endometrial epithelial cells (EECs) in context of endometrial fibrosis. We identified a typical type 2 epithelial-to-mesenchymal transition (EMT) in EECs from IUA patients and this process was induced by the forced expression of ΔNp63α in EECs. In transcriptomic analysis, we found that diverse signaling pathways regulated by ΔNp63α were involved in pro-EMT. We demonstrated that the DUSP4/GSK-3β/SNAI1 pathway was critical in transducing the pro-EMT signals initiated by ΔNp63α, while bFGF reversed ΔNp63α-induced EMT and endometrial fibrosis both in vitro and in vivo by blocking DUSP4/GSK3β/SNAI1 pathway. Taken together, our findings are important to understand the molecular mechanisms of endometrial fibrosis and to provide potential therapeutic targets.

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“…Since circASPH was determined to be a sponge of miR-370, we postulated that circASPH positively regulated HMGA2 by sponging miR-370. Generally, miRNAs regulate the posttranscriptional expression of target genes by specifically binding to the 3′-untranslated regions (3′-UTRs) 28 . Using TargetScan, we found a potential target site of miR-370 on the 3′-UTR of HMGA2 mRNA (Fig.…”

Section: Circasph Modulates the Expression Of Hmga2 A Direct Targetmentioning

confidence: 99%

HMGA2 regulates circular RNA ASPH to promote tumor growth in lung adenocarcinoma

Zhang³

et al. 2020

Cell Death Dis

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In this study, we identified a circular form of ASPH RNA (circASPH), expression of which was upregulated in lung adenocarcinoma and the human lung adenocarcinoma cell lines. We also found a positive correlation between circASPH level and the T and N stages of lung adenocarcinoma patients. Patients with higher levels of circASPH had a shorter overall survival. Moreover, we demonstrated that circASPH was directly regulated by HMGA2 and Twist1. The direct positive regulation of circASPH by Twist1 was dependent on the presence of HMGA2. Functional assays indicated that circASPH promoted the proliferation, migration, and invasion of lung adenocarcinoma cell lines in vitro. The promoting effect of tumor growth by circASPH was also observed in vivo. Mechanistically, circASPH was identified to act as a molecular sponge for miR-370 and abrogate miR-370-mediated inhibition of HMGA2. Finally, we demonstrated that the oncogenic function of circASPH was HMGA2-dependent. These findings reveal the oncogenic functions of the HMGA2-circASPH-HMGA2 axis and may be useful in developing circRNA-based therapeutic strategies for lung adenocarcinoma.

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miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4

Cited by 57 publications

References 45 publications

miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells

miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells

ΔNp63α-induced DUSP4/GSK3β/SNAI1 pathway in epithelial cells drives endometrial fibrosis

HMGA2 regulates circular RNA ASPH to promote tumor growth in lung adenocarcinoma

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