TGFβR2 is a major target of miR-93 in nasopharyngeal carcinoma aggressiveness

Lyu, Xiaoming; Fang, Weiyi; Cai, Longmei; Zheng, Hongliang; Ye, Yanfen; Zhang, Lan; li, Jinbang; Peng, Hong; Cho, William C.; Wang, Ena; Marincola, Francesco M.; Yao, Kangde; Cai, Hongwei; Li, Jiliang; Li, Xin

doi:10.1186/1476-4598-13-51

Cited by 88 publications

(84 citation statements)

References 69 publications

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“…miR-93 has been suggested to downregulate TGF-β signaling because miR-93 can reduce the expression of the mRNA for TGF-βR2 in breast cancer cells [30] and nasopharyngeal carcinoma cells [31]. However, we observed an upregulated TGF-β signaling by miR-93 in lung cancer cells, and this can be attributed to the downregulated NEDD4L.…”

Section: Discussioncontrasting

confidence: 54%

miR-93 promotes TGF-β-induced epithelial-to-mesenchymal transition through downregulation of NEDD4L in lung cancer cells

Han

Srivastava

et al. 2015

Tumor Biol.

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The level of microRNA-93 (miR-93) in tumors has been recently reported to be negatively correlated with survival of lung cancer patients. Considering that the most devastating aspect of lung cancer is metastasis, which can be promoted by transforming growth factor-β (TGF-β)-induced epithelial-to-mesenchymal transition (EMT), we sought to determine whether miR-93 is involved in this process. Here, we report that a previously unidentified target of miR-93, neural precursor cell expressed developmentally downregulated gene 4-like (NEDD4L), is able to mediate TGF-β-mediated EMT in lung cancer cells. miR-93 binds directly to the 3'-UTR of the NEDD4L messenger RNA (mRNA), leading to a downregulation of NEDD4L expression at the protein level. We next demonstrated that the downregulation of NEDD4L enhanced, while overexpression of NEDD4L reduced TGF-β signaling, reflected by increased phosphorylation of SMAD2 in the lung cancer cell line after TGF-β treatment. Furthermore, overexpression of miR-93 in lung cancer cells promoted TGF-β-induced EMT through downregulation of NEDD4L. The analysis of publicly available gene expression array datasets indicates that low NEDD4L expression correlates with poor outcomes among patients with lung cancer, further supporting the oncogenic role of miR-93 in lung tumorigenesis and metastasis.

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Section: Discussioncontrasting

confidence: 54%

miR-93 promotes TGF-β-induced epithelial-to-mesenchymal transition through downregulation of NEDD4L in lung cancer cells

Han

Srivastava

et al. 2015

Tumor Biol.

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“…MiR‐93‐5p has been acknowledged as a negative regulator of the immune response and can inhibit nuclear factor‐kappa B (NF‐ κ B) activation and proinflammatory cytokines (Lyu et al. 2014; Xu et al. 2014).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA regulation in an animal model of acute ocular hypertension

Wang

Valiente‐Soriano

Nadal-Nicolás

et al. 2016

Acta Ophthalmologica

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PurposeTo analyse miRNA regulation in a rat model of acute ocular hypertension (AOH).MethodsAcute ocular hypertension (AOH) was induced in the left eye of adult albino rats by inserting a cannula connected with a saline container into the anterior chamber. The contralateral eye served as a control. Seven days later, animals were killed. Retinas were used either for quantitative analysis of retinal ganglion cells (RGCs) and microglial cells or for miRNA array hybridization, qRT‐PCR and Western blotting.ResultsAnatomically, AOH caused axonal degeneration, a significant loss of RGCs and a significant increase in microglial cells in the ganglion cell layer. The miRNAs microarray analysis revealed 31 differentially expressed miRNAs in the AOH versus control group, and the regulation of 12 selected microRNAs was further confirmed by qRT‐PCR. Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated miRNAs. Of particular interest was the inflammatory pathway signalled by mitogen‐activated protein kinases (MAPKs). In agreement with the in silico analysis, p38 MAP kinase, tumour necrosis factor‐alpha (TNF‐α) and iNOS proteins were significantly upregulated in the AOH retinas.ConclusionsAcute IOP elevation led to changes in the expression of miRNAs, whose target genes were associated with the regulation of microglia‐mediated neuroinflammation or neural apoptosis. Addressing miRNAs in the process of retinal ischaemia and optic nerve damage in association with high IOP elevation may open new avenues in preventing retinal ganglion cell apoptosis and may serve as target for future therapeutic regimen in acute ocular hypertension and retinal ischaemic conditions.

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“…The aberrant expression of many miRNAs has been linked to human diseases including cancers. 7 To date, multiple cellular miRNAs, such as miR-148a, 8 miR-155, 9 miR-377, 10 miR-92a, 11 miR-200c, 12 miR-23a, 13 miR-130b, 14 miR-30a, 15 miR-149 16 and miR-93 17 have been reported to modulate the EMT and metastasis in various cancers, but only three of them are implicated in the EMT in nasopharyngeal carcinoma (NPC), a malignancy typically featured by its early metastasis and invasion. [17][18][19] Therefore, it is necessary to identify other unknown miRNAs that regulate the EMT and metastasis of NPC cells.…”

Section: Introductionmentioning

confidence: 99%

EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN

et al. 2014

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The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.

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TGFβR2 is a major target of miR-93 in nasopharyngeal carcinoma aggressiveness

Cited by 88 publications

References 69 publications

miR-93 promotes TGF-β-induced epithelial-to-mesenchymal transition through downregulation of NEDD4L in lung cancer cells

miR-93 promotes TGF-β-induced epithelial-to-mesenchymal transition through downregulation of NEDD4L in lung cancer cells

MicroRNA regulation in an animal model of acute ocular hypertension

EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN

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