Abstract
BackgroundAccumulating evidence has suggested that aberrant expression of long non-coding RNAs (lncRNAs) may contribute to cancer progression in association with radioresistance. The current study aimed to identify the potential role of lncRNA MAGI2-AS3 and the underlying mechanism in its regulation of the radio-sensitivity of esophageal cancer cells.Methods and ResultsInitially, we detected high expression of HOXB7 from microarray-based gene expression profiling of esophageal cancer. Then, we identified the interactions among MAGI2-AS3, HOXB7, and EZH2 by dual-luciferase reporter gene assay, RNA pull-down assay, RIP assay and ChIP assay. HOXB7 was highly-expressed, while MAGI2-AS3 was poorly-expressed in esophageal cancer tissues and cells. The effect of MAGI2-AS3 and HOXB7 on esophageal cancer cell proliferation and apoptosis as well as tumorigenicity of radioresistant cells was examined by gain- and loss-of-function experiments. Interestingly, MAGI2-AS3 down-regulated HOXB7 through interaction with EZH2, which promoted cell apoptosis and inhibited proliferation and radio-resistance. Besides, down-regulation of MAGI2-AS3 exerted a promoting effect on these malignant phenotypes.ConclusionTaken together, our results reveal the potential role of MAGI2-AS3 over-expression in controlling esophageal cancer resistance to radiotherapy by down-regulating HOXB7, this providing a candidate biomarker for resistance to radiotherapy.
Highlights
MATERIALS AND METHODSEsophageal cancer is one of the most aggressive gastrointestinal cancers and one of the leading causes of cancer-related deaths across the world, placing a substantial burden on the quality of life among patients undergoing treatment (Lagergren et al, 2017)
A heat map illustrating the most DEGs is shown in Figure 1A, which depicts that HOXB7 was the most significantly highly differentially expressed gene in esophageal cancer
The GEPIA2 database5 was used to retrieve the expression of HOXB7 in esophageal cancer included in the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases, which revealed a markedly abundant expression of HOXB7 in esophageal cancer (Figure 1B)
Summary
MATERIALS AND METHODSEsophageal cancer is one of the most aggressive gastrointestinal cancers and one of the leading causes of cancer-related deaths across the world, placing a substantial burden on the quality of life among patients undergoing treatment (Lagergren et al, 2017). Current mainstay treatment modalities include targeted therapies, immunotherapies, resection, chemoradiotherapy, and preoperative chemotherapy (Hamamoto et al, 2018; Barsouk et al, 2019). These therapies have significantly improved the survival for early stage patients, a large proportion of patients plagued by metastatic esophageal cancer still exhibit poor survival rates (Barsouk et al, 2019). Accumulating evidence has indicated that primary tumor directed radiotherapy is associated with the overall survival improvement in patients with newly diagnosed metastatic esophageal cancer (Guttmann et al, 2017). The current study aimed to identify the potential role of lncRNA MAGI2AS3 and the underlying mechanism in its regulation of the radio-sensitivity of esophageal cancer cells
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