miR-18a promotes malignant progression by impairing microRNA biogenesis in nasopharyngeal carcinoma

Luo, Zhaohui; Dai, Yu; zhang, Liyang; Jiang, Chen Chen; Li, Zheng; Yang, Jianbo; McCarthy, James B.; She, Xiaoling; Zhang, Wenling; Ma, Jian; Wang, Xiong; Wu, Minghua; Lu, Jianhong; Li, Xiayu; Li, Xiaoling; Xiang, Juanjuan; Li, Guiyuan

doi:10.1093/carcin/bgs329

Cited by 109 publications

(94 citation statements)

References 46 publications

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“…miR-18a is located in the chromosome 13q31.1 region and belongs to the miR-17-92 cluster (22). A high expression of miR-18a has been found in several cancer types, such as bladder cancer (23), hepatocellular carcinoma (24), colon cancer (25) and nasopharyngeal carcinoma (26). The function of miR-18a in those types of cancer is as oncogene or suppressor.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-18a enhances the radiosensitivity of cervical cancer cells by promoting radiation-induced apoptosis

Pan

Yang

et al. 2015

Oncology Reports

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Abstract. Evidence has demonstrated that microRNAs (miRNAs) are important in the regulation of cellular radiosensitivity of various types of human cancer. The aim of this study was to examine the role of miR-18a in regulating the radiosensitivity of cervical cancer, in order to understand the underlying mechanism and to assess the potential of miR-18a as a biomarker for predicting radiosensitivity. The expression of miR-18a was investigated in 48 cervical cancer patients. The results revealed that miR-18a expression was significantly higher in radiosensitive patients than in radioresistant patients by RT-qPCR (P<0.05). Transient transfection experiments showed that miR-18a was upregulated by the miR-18a mimic and downregulated by the miR-18a inhibitor in the SiHa and HeLa cells. Without irradiation treatment, a similar growth was observed in the cells with or without transfection of miR-18a. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Hoechst staining assays showed that miR-18a had no effect on the proliferation and apoptosis of cervical cancer cells after transfection. However, the upregulation of miR-18a suppressed the level of ataxia-telangiectasia mutated and attenuated DNA double-strand break repair after irradiation, which re-sensitized the cervical cancer cells to radiotherapy by promoting apoptosis. Taken together, these results demonstrated that miR-18a is a potential molecule predictor of radiosensitivity in cervical cancer patients and played an important role in the response to radiotherapy.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-18a enhances the radiosensitivity of cervical cancer cells by promoting radiation-induced apoptosis

Pan

Yang

et al. 2015

Oncology Reports

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“…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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“…Conversely, ERalpha also binds to c-MYC and in turn upregulates the expression of pre-miR-18a in an estrogen-dependent manner [34]. In nasopharyngeal carcinoma, miR-18a was reported to negatively regulate Dicer1 expression and promote the growth, migration and invasion of nasopharyngeal cancer cells, which consequently causes the global downregulation of miRNA expression levels [35].…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancer

et al. 2014

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Background Recently, circulating microRNAs have been reported to be stably detectable in plasma/serum and to function as potent non-invasive biomarkers in various cancers. We hypothesized that miR-18a could contribute to a novel plasma biomarker in patients with gastric cancer (GC). Methods We focused on miR-18a, which is a component of miR-17-92 cluster and has been reported as highly expressed in GC tissues. The study involved three steps: (1) confirmation of the higher miR-18a expression in primary GC tissues and GC cell lines than in normal gastric tissues and a fibroblast cell line; (2) evaluation of the plasma miR18a assay using quantitative RT-PCR by comparing 104 GC patients and 65 healthy volunteers; (3) evaluation of monitoring tumor dynamics by the plasma miR-18a assay. Results (1) The miR-18a expressions were significantly higher in GC tissues than in normal gastric tissues (P = 0.0286) and higher in all examined GC cell lines than in the fibroblast cell line. (2) The plasma miR-18a concentrations were significantly higher in GC patients than in healthy controls (P \ 0.0001). The value of the area under the receiver-operating characteristic curve was 0.8059. (3) The plasma miR-18a levels were significantly reduced in postoperative samples compared to in preoperative samples (P = 0.0002). In an miR-18a overexpressing cell line, the miR-18a concentration of cultured medium increased in both cell number and time-course dependent manners, suggesting microRNA might be released from cancer cells into the surrounding environment. Conclusions Circulating miR-18a could be a useful biomarker for screening GC and monitoring tumor dynamics.

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miR-18a promotes malignant progression by impairing microRNA biogenesis in nasopharyngeal carcinoma

Cited by 109 publications

References 46 publications

MicroRNA-18a enhances the radiosensitivity of cervical cancer cells by promoting radiation-induced apoptosis

MicroRNA-18a enhances the radiosensitivity of cervical cancer cells by promoting radiation-induced apoptosis

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

Circulating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancer

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