Details

Autor(en) / Beteiligte

• Sharma, Rinu

Titel

Abstract 5453: Dysregulation of miRNAs in esophageal cancer: function and clinical implication

Ist Teil von

• Cancer research (Chicago, Ill.), 2017-07, Vol.77 (13_Supplement), p.5453-5453

Erscheinungsjahr

2017

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Abstract Background: Growing evidence suggests importance of aberrant microRNA (miRNA) expression in development and progression of cancer. Recent studies have demonstrated the potential of miRNA panels as promising diagnostic, prognostic and predictive biomarkers. Objective: The purpose of the present study was to evaluate the clinical and functional significance of miRNAs in esophageal cancer (EC). Methods: Herein, we evaluated the diagnostic potential of a five miRNA panel (consisting of miR-21, miR-144, miR-107, miR-93 and miR-342) in EC detection using quantitative real time PCR (qRTPCR). To evaluate the discriminatory power of miRNA panel, receiver operating characteristic curve (ROC) curves were generated for each of the miRNAs followed by risk score analysis. Briefly, linear regression models were fitted using the cancer status and each of the risk score as input. ROC curves were then used to evaluate the diagnostic potential of the panel and to find out the appropriate cut-off point. Sensitivity and specificity of the panel were then determined. Further, pathway enrichment analysis was carried out to find the most significant pathways targeted by these miRNAs. Next, we elucidated the role of miR-144, by silencing it in KYSE-410 cells followed by MTT assay, cell cycle analysis, colony formation assay and scratch assay. Potential targets of miR-144 were predicted by in silico approach followed by in vitro validation by luciferase reporter assay. Results: The ROC curve analysis indicated that the panel of five miRNAs (AUC=0.851, p<0.001) constitutes a more sensitive and specific diagnostic marker as compared to any of the single miRNAs. Most importantly, panel of circulating miRNAs showed enhanced sensitivity (87.5%) and specificity (90.4%) with an AUC of 0.96 (p<0.001) in discriminating EC patients from normal subjects. Inhibition of miR-144 significantly suppressed the proliferation of ESCC cells by 42.085±1.73% at 72 h post transfection. Moreover, knockdown of miR-144 decreased (p=0.046) the migration potential of KYSE-410 cells as compared to the cells treated with negative control. In silico analysis and further validation by dual-luciferase reporter assay revealed PURA to be a direct downstream target of miR-144. Conclusion: Herein, we have demonstrated the potential diagnostic implication of five miRNA panel. Further, we have shown that mir-144 acts as an oncogenic miRNA by targeting PURA and promotes EC cell proliferation. Citation Format: Rinu Sharma. Dysregulation of miRNAs in esophageal cancer: function and clinical implication [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5453. doi:10.1158/1538-7445.AM2017-5453