title: Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma.
abstract: Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3'UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Miao
authors.initials: M
authors.lastname: Yang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Meng
authors.forename: Juan
authors.initials: J
authors.lastname: Liao
authors.forename: Jingyi
authors.initials: J
authors.lastname: Sheng
authors.forename: Yuepu
authors.initials: Y
authors.lastname: Pu
authors.forename: Lihong
authors.initials: L
authors.lastname: Yin
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C475820:CCNE1 protein, human; D019927:Cyclin E; C555098:MIRN139 microRNA, human; D035683:MicroRNAs; C082631:NR5A2 protein, human; D015513:Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D020780:Matrix Metalloproteinase 9