Down-Regulation of MiR-1294 is Related to Dismal Prognosis of Patients with Esophageal Squamous Cell Carcinoma through Elevating C-MYC Expression

Li, Kai; Li, Liyi; Rusidanmu, Aizemaiti; Wang, Yongqing; Lv, Xiaoshu

doi:10.1159/000374056

Cited by 37 publications

(31 citation statements)

References 14 publications

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“…The cell proliferation was detected using MTT assay as described previously [14]. Briefly, the transfected SCC-4 cells were seeded in a 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-375 Inhibits Growth and Enhances Radiosensitivity in Oral Squamous Cell Carcinoma by Targeting Insulin Like Growth Factor 1 Receptor

Zhang

Hou

et al. 2017

Cell Physiol Biochem

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Background: MicroRNAs (miRNAs) have emerged as key players in various human biological processes, including tumorigenesis. Here, we investigated the roles of miR-375 in the pathogenesis of oral squamous cell carcinoma (OSCC). Methods: We performed quantitative real-time PCR (qRT-PCR) to detect miR-375 expression in OSCC tissues and corresponding normal oral epithelial tissues and analyze the correlation of miR-375 expression with OSCC metastasis and patient’s survival. Then, the effects of miR-375 expression on proliferation, cell cycle, apoptosis and radiosensitivity in OSCC cells were determined by using MTT, flow cytometry and clonogenic survival assays. A dual-luciferase reporter assay was performed to test whether miR-375 binds to the 3’-untranslated region (3’-UTR) of target mRNA. Results: The expression level of miR-375 in OSCC tissues was significantly lower than that in normal oral epithelial tissues, and low miR-375 expression was correlated with higher incidence of lymph node metastasis and poor survival of OSCC patients. Upregulation of miR-375 significantly inhibits growth, induces cell cycle arrest in G₀/G₁ phase, increases apoptosis and enhances radiosensitivity in OSCC cells. Analysis of luciferase activity demonstrated that miR-375 binds to the 3’-UTR of insulin like growth factor 1 receptor (IGF-1R). Small interfering RNA (shRNA)-mediated IGF-1R knockdown mimics the effects of miR-375 upregulation, while overexpression of IGF-1R partially reverses those effects in OSCC cells. Conclusion: It was obviously demonstrated that miRNA-375 inhibits growth and enhances radiosensitivity in OSCC cells by targeting IGF-1R, suggesting that miR-375 may be a potential therapeutic target for OSCC patients.

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“…The cell proliferation was detected using MTT assay as described previously [14]. Briefly, the transfected SCC-4 cells were seeded in a 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-375 Inhibits Growth and Enhances Radiosensitivity in Oral Squamous Cell Carcinoma by Targeting Insulin Like Growth Factor 1 Receptor

Zhang

Hou

et al. 2017

Cell Physiol Biochem

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“…Oesophageal squamous cell carcinoma (ESCC) is one of the most common malignancy worldwide and is the most common subtype of oesophageal cancer in Asian countries [1][2]. miRNAs (19)(20)(21)(22)(23)(24)(25) nucleotides non-coding single stranded RNA) could play a critical role in the regulation of pathogenesis of the oesophageal cancer by regulating the expression of growth related target genes [3][4][5][6]. MicroRNA-498 (miR-498) is located intergenically in 19q13.42 and play critical roles in the pathogenesis of different carcinomas including colorectal, breast, lung, ovarian and thyroid as well as in acute myeloid leukaemia and Kaposi's sarcoma [7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

MiR-498 in esophageal squamous cell carcinoma: clinicopathological impacts and functional interactions

et al. 2017

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MicroRNA-498 plays a crucial role in progression of many carcinomas. The signaling pathways by which miR-498 modulates carcinogenesis are still unknown. Also, miR-498-associated molecular pathogenesis has never been studied in esophageal squamous cell carcinoma (ESCC). Herein, we aimed to examine the expression and functional roles of miR-498 in ESCC as well as its influences on the clinicopathological features in patients with ESCC. Expression of miR-498 was investigated in 93 ESCC tissues and 5 ESCC cell lines using quantitative real-time polymerase chain reaction. In vitro effects of miR-498 on cellular process were studied followed by overexpression of miR-498. Western blot and immunofluorescence techniques were used to identify the interacting targets for miR-498 in ESCC. miR-498 expression was significantly reduced in ESCC when compared with the nonneoplastic esophageal tissues (P<.05). Patients with low miR-498 expression showed different histological grading of cancer and survival rates when compared with the patients with high miR-498 expression. Overexpression of miR-498 in ESCC cell lines induced remarkable reductions of cell proliferation, barrier penetration, and colony formation when compared with control and wild-type counterparts. Also, miR-498 activated the FOXO1/KLF6 transcriptional axis in ESCC. In addition, miR-498 overexpression increased p21 protein expression and led to reduced cancer cell growth. To conclude, reduced expression of miR-498 in ESCC and in vitro analysis have confirmed the tumor suppressor properties of miR-498 by modulating the FOXO1/KLF6 signaling pathway. The changes in miR-498 expression may have impacts on the clinical pathological parameters of ESCC as well as in the management of the patients with ESCC.

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“…Moreover, it has been demonstrated that the miRNA profile of tissues exhibits characteristic changes in certain types of tumors [19,20]. A number of miRNAs have been shown to participate in tumor progression, invasion, and metastasis, including miR-134 [21], miR-145 [22], miR-625 [23], and miR1294 [24]. However, due to clinical heterogeneity, sample insufficiency, and use of various data processing methods, there is inconsistency in the results of these studies.…”

Section: Discussionmentioning

confidence: 99%

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma

Zhang

Dai

2020

BioMed Research International

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Objective. We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). Results. With cut-off criteria of P<0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan–Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. Conclusions. Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.

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Down-Regulation of MiR-1294 is Related to Dismal Prognosis of Patients with Esophageal Squamous Cell Carcinoma through Elevating C-MYC Expression

Cited by 37 publications

References 14 publications

MicroRNA-375 Inhibits Growth and Enhances Radiosensitivity in Oral Squamous Cell Carcinoma by Targeting Insulin Like Growth Factor 1 Receptor

MicroRNA-375 Inhibits Growth and Enhances Radiosensitivity in Oral Squamous Cell Carcinoma by Targeting Insulin Like Growth Factor 1 Receptor

MiR-498 in esophageal squamous cell carcinoma: clinicopathological impacts and functional interactions

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma

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