Wenpeng Jiao1, Jinyan Zhang2, Yuanyuan Wei3, Junhua Feng4, Ming Ma5, Hongzheng Zhao6, Lihong Wang7, Wenjing Jiao8. 1. Dept. of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address: jiaowenpeng163@163.com. 2. Clinical Laboratory, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address: jinyanzhang66@163.com. 3. Dept. of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address: jysy0101@126.com. 4. Clinical Laboratory, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address: 13833478260@163.com. 5. Clinical Laboratory, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address: maming19830419@163.com. 6. Clinical Laboratory, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address: 56178603@qq.com. 7. Clinical Laboratory, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address: wlh.19630704@163.com. 8. Clinical Laboratory, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address: wenjing-79@163.com.
Abstract
BACKGROUND: MiR-139-5p plays a significant role in tumorigenesis, metastasis and recurrence, suggesting that it may potentially be used as a promising biomarker for esophageal cancer diagnosis, prognosis and therapy. This study aimed to investigate the role and the mechanism of miRNA-139-5p in esophageal cancer. METHODS: This study included 11 patients from an area with a high incidence of esophageal cancer. The expression levels of miRNA-139-5p in esophageal cancer tissues and para-carcinoma tissues of 11 patients were measured. We examined the expression of miR-139-5p in serum obtained from 92 consecutive patients from Cixian, which is a region in Hebei Province with a high rate of histologically confirmed esophageal cancer. The expression of miR-139-5p in esophageal cancer cell lines was detected. In the KYSE150 cell line with the lowest expression level of miR-139-5p, we transfected a plasmid to upregulate the expression level and examined the role of miR-139-5p in esophageal squamous cell carcinoma proliferation, migration and invasion. We conducted a gene profiling study using miR-139-5p cell lines to detect the expression of significant genes related to tumor progression, including cyclinD1, E-cadherin and VEGFR-1. We then constructed luciferase reporters containing miR-139-5p, which contained wild-type (WT) or mutated-type (Mut) VEGFR-1 binding sites to investigate the target. RESULTS: MiRNA-139-5p expression levels in esophageal cancer tissues from 11 patients were significantly higher than those in para-carcinoma tissues. MiR-139-5p expression in the serum of 92 patients with esophageal cancer was associated with gender (P = 0.039) and TNM stage (P = 0.015). Factors that were not correlated with miR-139-5p expression were age (P = 0.293), smoking history (P = 0.397), length of tumor (P = 0.309), width of tumor (P = 0.296), depth of tumor (P = 0.724), lymphoma metastasis (P = 0.531) and postoperative therapy (P = 0.884). MiR-139-5p (P = 0.013) correlated significantly with observed survival rates. The lymphoma metastasis (P = 0.005) and TNM stage (P = 0.000) were significantly associated with observed survival rates. However, no significant relationships were found between the miR-139-5p and patient characteristics including gender, age, smoking history, tumor size and postoperative therapy. In the KYSE150 cell line, the expression level of miR-139-5p was the lowest. We transfected a plasmid to upregulate the expression level and found that the cell proliferation, metastasis and invasion abilities decreased. Upregulation of miR-139-5p inhibited the expression of Cyclin D1 and VEGFR-1 and increased the expression of E-cadherin. For further confirmation, we constructed luciferase reporters containing miR-139-5p, which contained wild-type (WT) or mutated-type (Mut) VEGFR-1 binding sites for target investigation. The results show that the corresponding VEGFR-1-Mut construct no longer suppressed miR-139-5p. CONCLUSIONS: MiR-139-5p may be a novel therapeutic target and prognostic biomarker of esophageal cancer.
BACKGROUND:MiR-139-5p plays a significant role in tumorigenesis, metastasis and recurrence, suggesting that it may potentially be used as a promising biomarker for esophageal cancer diagnosis, prognosis and therapy. This study aimed to investigate the role and the mechanism of miRNA-139-5p in esophageal cancer. METHODS: This study included 11 patients from an area with a high incidence of esophageal cancer. The expression levels of miRNA-139-5p in esophageal cancer tissues and para-carcinoma tissues of 11 patients were measured. We examined the expression of miR-139-5p in serum obtained from 92 consecutive patients from Cixian, which is a region in Hebei Province with a high rate of histologically confirmed esophageal cancer. The expression of miR-139-5p in esophageal cancer cell lines was detected. In the KYSE150 cell line with the lowest expression level of miR-139-5p, we transfected a plasmid to upregulate the expression level and examined the role of miR-139-5p in esophageal squamous cell carcinoma proliferation, migration and invasion. We conducted a gene profiling study using miR-139-5p cell lines to detect the expression of significant genes related to tumor progression, including cyclinD1, E-cadherin and VEGFR-1. We then constructed luciferase reporters containing miR-139-5p, which contained wild-type (WT) or mutated-type (Mut) VEGFR-1 binding sites to investigate the target. RESULTS: MiRNA-139-5p expression levels in esophageal cancer tissues from 11 patients were significantly higher than those in para-carcinoma tissues. MiR-139-5p expression in the serum of 92 patients with esophageal cancer was associated with gender (P = 0.039) and TNM stage (P = 0.015). Factors that were not correlated with miR-139-5p expression were age (P = 0.293), smoking history (P = 0.397), length of tumor (P = 0.309), width of tumor (P = 0.296), depth of tumor (P = 0.724), lymphoma metastasis (P = 0.531) and postoperative therapy (P = 0.884). MiR-139-5p (P = 0.013) correlated significantly with observed survival rates. The lymphoma metastasis (P = 0.005) and TNM stage (P = 0.000) were significantly associated with observed survival rates. However, no significant relationships were found between the miR-139-5p and patient characteristics including gender, age, smoking history, tumor size and postoperative therapy. In the KYSE150 cell line, the expression level of miR-139-5p was the lowest. We transfected a plasmid to upregulate the expression level and found that the cell proliferation, metastasis and invasion abilities decreased. Upregulation of miR-139-5p inhibited the expression of Cyclin D1 and VEGFR-1 and increased the expression of E-cadherin. For further confirmation, we constructed luciferase reporters containing miR-139-5p, which contained wild-type (WT) or mutated-type (Mut) VEGFR-1 binding sites for target investigation. The results show that the corresponding VEGFR-1-Mut construct no longer suppressed miR-139-5p. CONCLUSIONS:MiR-139-5p may be a novel therapeutic target and prognostic biomarker of esophageal cancer.