School of Medicine and Health Sciences Poster Presentations
miR-196b is a Potential Biomarker for Human Esophageal Cancer
Document Type
Poster
Keywords
Cancer early detection; Innovative; Therapeutic
Publication Date
Spring 2017
Abstract
Esophageal cancer is the sixth most common cause of cancer related death. Although multiple genetic and epigenetic alterations have been detected in esophageal cancer, molecular markers for early diagnosis and prediction of prognosis or treatment responses are quite limited. microRNA (miRNA) is a class of small-regulatory non-coding RNA, acting as either a tumor suppressor or oncogene by regulating gene expression through pairing with complementary seed of the targeted messenger RNAs (mRNA). A number of miRNA expression profiling studies have been conducted in esophageal cancer. By cross-referencing esophageal cancer data with miRNA expression profiling, we identify a group of dysregulated miRNAs in esophageal cancer, including upregulated miR-196b and miR-135a, and downregulated miR-141, miR-200a-5p, miR-200b-3p, miR-27b, miR-210. We first assessed the expression of miRNAs in esophageal cancer cell lines and primary esophageal cancer tissues by real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). Significantly overexpression of miR-196b was observed in human esophageal cell lines KYSE-70 and KYSE-180 compared with normal esophageal squamous cell line HET-1A. Furthermore, the overexpressed miR-196b was detected in 12 out of 14 (86%) cancer tissues compared with matched normal tissues. TargetScan and miRanda bioinformatics tools were used to identify target genes of miR-196b. A list of targets was obtained, including ephrin type-A receptor 7 (EPHA7), one of members of the ephrin receptor (EPH) subfamily of the protein-tyrosine kinase family. We found a significant inverse correlation between miR-196b and EPHA7 expression in both cell lines and tissues. Luciferase assays revealed that miR-196b directly targets the 3'-UTR of EPHA7 gene. Forced expression of miR-196b resulted in significant downregulation of EPHA7 and promoted the proliferation and invasion in KYSE-70 and KYSE-180 cells. It has been reported that low EphA7 expression correlated with lymph node metastasis and poor prognosis for esophageal cancer. These indicate that EPHA7 may function as a tumor suppressor with immediate therapeutic potential. Our data suggest that miR-196b acts as an oncomiR by downregulating EPHA7 in esophageal cancer. Inhibition of miR-196b may improve anti-tumor efficiency by restoring the expression of EPHA7. Therefore, miR-196b might serves as a therapeutic target for esophageal cancer.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Open Access
1
miR-196b is a Potential Biomarker for Human Esophageal Cancer
Esophageal cancer is the sixth most common cause of cancer related death. Although multiple genetic and epigenetic alterations have been detected in esophageal cancer, molecular markers for early diagnosis and prediction of prognosis or treatment responses are quite limited. microRNA (miRNA) is a class of small-regulatory non-coding RNA, acting as either a tumor suppressor or oncogene by regulating gene expression through pairing with complementary seed of the targeted messenger RNAs (mRNA). A number of miRNA expression profiling studies have been conducted in esophageal cancer. By cross-referencing esophageal cancer data with miRNA expression profiling, we identify a group of dysregulated miRNAs in esophageal cancer, including upregulated miR-196b and miR-135a, and downregulated miR-141, miR-200a-5p, miR-200b-3p, miR-27b, miR-210. We first assessed the expression of miRNAs in esophageal cancer cell lines and primary esophageal cancer tissues by real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). Significantly overexpression of miR-196b was observed in human esophageal cell lines KYSE-70 and KYSE-180 compared with normal esophageal squamous cell line HET-1A. Furthermore, the overexpressed miR-196b was detected in 12 out of 14 (86%) cancer tissues compared with matched normal tissues. TargetScan and miRanda bioinformatics tools were used to identify target genes of miR-196b. A list of targets was obtained, including ephrin type-A receptor 7 (EPHA7), one of members of the ephrin receptor (EPH) subfamily of the protein-tyrosine kinase family. We found a significant inverse correlation between miR-196b and EPHA7 expression in both cell lines and tissues. Luciferase assays revealed that miR-196b directly targets the 3'-UTR of EPHA7 gene. Forced expression of miR-196b resulted in significant downregulation of EPHA7 and promoted the proliferation and invasion in KYSE-70 and KYSE-180 cells. It has been reported that low EphA7 expression correlated with lymph node metastasis and poor prognosis for esophageal cancer. These indicate that EPHA7 may function as a tumor suppressor with immediate therapeutic potential. Our data suggest that miR-196b acts as an oncomiR by downregulating EPHA7 in esophageal cancer. Inhibition of miR-196b may improve anti-tumor efficiency by restoring the expression of EPHA7. Therefore, miR-196b might serves as a therapeutic target for esophageal cancer.
Comments
Poster to be presented at GW Annual Research Days 2017.