miR-296-3p Negatively Regulated by Nicotine Stimulates Cytoplasmic Translocation of c-Myc via MK2 to Suppress Chemotherapy Resistance

Deng, Xiaojie; Liu, Zhen; Liu, Xiong; Fu, Qiangqiang; Deng, Tongyuan; Lü, Juan; Liu, Yiyi; Liang, Zhonglin; Jiang, Qingping; Chen, Cheng; Fang, Weiyi

doi:10.1016/j.ymthe.2018.01.023

Cited by 44 publications

(41 citation statements)

References 57 publications

(66 reference statements)

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“…in the present study, the expression of key proteins of Pi3K/aKT, ras and Wnt signaling was determined following the downregulation of mir-296-3p in GBM. The downregulation of Wnt signaling was only observed in GBM cells (43,44), but the observation excluded the previously reported regulatory association between mir-296-3p and c-Myc. The results of the present study indicated that mir-296-3p promoted c-Myc expression via activating the Wnt signaling.…”

Section: Discussioncontrasting

confidence: 68%

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miR‑296‑3p promotes the proliferation of glioblastoma cells by targeting ICAT

Zhou

2020

Mol Med Report

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Micrornas (mirna/mirs) serve an important function in the regulation of gene expression, and have been indicated to mediate a number of cellular biological processes, including cell proliferation, the cell cycle, cell apoptosis and cell differentiation. The altered expression of mirnas has been revealed to result in a variety of human diseases, including glioblastoma multiforme (GBM). The present study indicated an increase in mir-296-3p in glioma tumor types compared with normal brain, particularly in the samples from patients with high grade GBM. antagonizing mir-296-3p was demonstrated to induce cell growth arrest and cell cycle redistribution in u251 cells. The mir-296-3p antagonist altered the expression of a number of key genes that are involved in cell cycle control, including cyclin d1 and p21. additionally, the decrease of mir-296-3p increased inhibitor of β-catenin and T cell factor (icaT) expression, and increased mir-296-3p-inhibited icaT expression in u251 cells. Bioinformatics analysis indicated that icaT is a target gene of mir-296-3p, which was further validated using a dual-luciferase reporter assay. Through the regulation of icaT, the mir-296-3p antagonist decreased β-catenin protein expression and increased the expression of its target genes. Silencing icaT was indicated to reverse the mir-296-3p downregulation-induced inactivation of Wnt signaling and cell growth arrest in glioma cells. The present study also indicated a negative correlation between icaT mrna levels and mir-296-3p levels in glioma tumor types. In conclusion, the present study identified an oncogenic function of mir-296-3p in glioblastoma via the direct regulation of icaT.

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Section: Discussioncontrasting

confidence: 68%

“…been suggested to target MK2 and PrKca in nasopharyngeal carcinoma and lung adenocarcinoma, respectively (43,44). The downregulation of MaPK activated protein kinase 2 and protein kinase cα was observed to inhibit Pi3K/aKT and ras signaling, resulting in the downregulation of c-Myc (43,44).…”

Section: Discussionmentioning

confidence: 99%

miR‑296‑3p promotes the proliferation of glioblastoma cells by targeting ICAT

Zhou

2020

Mol Med Report

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“…We demonstrated that expression of VPS33B was significantly reduced in DSS/AOM‐induced mice CRC models. Furthermore, we also observed that VPS33B was suppressed by nicotine, a key component of tobacco, which is known as a carcinogen and closely associated with cancers including CRC via RAS/ERK/c‐Jun‐induced transcription suppression of VPS33B promoter in human CRC cells. These data suggest that VPS33B can be damaged by chemical carcinogens and participates in CRC pathogenesis.…”

Section: Discussionmentioning

confidence: 62%

VPS33B negatively modulated by nicotine functions as a tumor suppressor in colorectal cancer

Chen

Liu

Wang

et al. 2019

Intl Journal of Cancer

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The biological role of vacuolar protein sorting 33B (VPS33B) has not been examined in colorectal cancer (CRC). We report that VPS33B was downregulated in dextran sulfate sodium/azoxymethane (DSS/AOM) ‐induced CRC mice models and nicotine‐treated CRC cells via the PI3K/AKT/c‐Jun pathway. Reduced VPS33B is an unfavorable factor promoting poor prognosis in human CRC patients. VPS33B overexpression suppressed CRC proliferation, intrahepatic metastasis and chemoresistance of cisplatin (DDP) in vivo and in vitro through modulating the epidermal growth factor receptor (EGFR)/RAS/ERK/c‐Myc/p53/miR‐133a‐3p feedback loop and the downstream cell cycle or EMT‐related factors. Furthermore, NESG1 as a newly identified tumor suppressor interacted with VPS33B via colocalization in the cytoplasm, and it was stimulated by VPS33B through the downregulation of RAS/ERK/c‐Jun‐mediated transcription. NESG1 also activated VPS33B expression via the RAS/ERK/c‐Jun pathway. Suppression of NESG1 increased cell growth, migration and invasion via the reversion of the VPS33B‐modulating signal in VPS33B‐overexpressed cells. Taken together, VPS33B as a tumor suppressor is easily dysregulated by chemical carcinogens and it interacts with NESG1 to modulate the EGFR/RAS/ERK/c‐Myc/p53/miR‐133a‐3p feedback loop and thus suppress the malignant phenotype of CRC.

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“…Consistent with our results, underexpression of miR-296 may cause tumor progression by inducing EMT events in some tumor cells [33,34]. miR-296 negatively regulated by nicotine directly targets mitogen-activated protein kinase-activated protein kinase-2-induced Ras/Braf/Erk/Mek/c-Myc or Phosphoinositide 3-kinase (PI3K)/Protein Kinase B(AKT)/c-Myc signaling to stimulate its own expression and suppress NPC cell proliferation and metastasis [35].…”

Section: Discussionmentioning

confidence: 85%

Involvement of MicroRNA-296 in the Inhibitory Effect of Epigallocatechin Gallate against the Migratory Properties of Anoikis-Resistant Nasopharyngeal Carcinoma Cells

Lin

Wang

Chen

et al. 2020

Cancers

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Short noncoding endogenous RNAs, including microRNAs (miRNAs), are associated with the development and metastasis of multiple cancers. Epigallocatechin gallate (EGCG), the most active and abundant polyphenol in green tea, plays a crucial role in the modulation of miRNA expression, which is related to changes in cancer progression. In the present study, we explore whether EGCG exerts its suppressive effects on nasopharyngeal carcinoma (NPC) cells through miRNA regulation. The anoikis-resistant sphere-forming NPC cells grown under anchorage-independent conditions exhibit enhanced migratory properties, which were inhibited by EGCG treatment. The miR-296 level was lower in the anoikis-resistant cells than in the monolayer parental cells; however, miR-296 was significantly upregulated after EGCG treatment. We demonstrate that miR-296 is involved in the inhibitory effects of EGCG on the anoikis-resistant NPC cells through the downregulation of signal transducer and activator of transcription 3 (STAT3) activation. Our study is the first to demonstrate that EGCG inhibited the migratory properties of anoikis-resistant cells by modulating the expression of miRNA in NPC cells. Our results indicate the novel effects of EGCG on miRNA regulation to inhibit an invasive phenotype of NPC as well as the regulatory role of miR-296.

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miR-296-3p Negatively Regulated by Nicotine Stimulates Cytoplasmic Translocation of c-Myc via MK2 to Suppress Chemotherapy Resistance

Cited by 44 publications

References 57 publications

miR‑296‑3p promotes the proliferation of glioblastoma cells by targeting ICAT

miR‑296‑3p promotes the proliferation of glioblastoma cells by targeting ICAT

VPS33B negatively modulated by nicotine functions as a tumor suppressor in colorectal cancer

Involvement of MicroRNA-296 in the Inhibitory Effect of Epigallocatechin Gallate against the Migratory Properties of Anoikis-Resistant Nasopharyngeal Carcinoma Cells

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