STAT3 is involved in miR-124-mediated suppressive effects on esophageal cancer cells.
BACKGROUND
Esophageal cancer (EC) is one of the most common cancers worldwide. The cancer-related inflammation pathway- signal transducer and activator of transition 3 (STAT3) signaling pathway has been reported to play critical role in its initiation and progression, while the way mediated its hyperactivation remains elusive so far. Accumulating studies reported the important role of microRNAs (miRNAs) in the regulation of gene expression, among of which, the miR-124/STAT3 interaction has been widely reported in various cancers, while its role in EC has not been investigated yet.


METHODS
Firstly, we identified the target role of STAT3 in esophageal cancers using Dual-luciferase reporter assays. Next, we explored the expression of miR-124 in EC tissues. To further investigate its effects on the malignant phenotype of EC cells, we completed a series of experiments. Through transfection with miR-124 mimic, the expression of miR-124 in esophageal cancer cell lines, Eca109 and TE-1, were restored. Next, we detected the effects of ectopic miR-124 expression on the proliferation, cell cycle distribution, apoptosis, migration and invasion of EC cells in vitro, and the tumor growth in vivo.


RESULTS
Dual-luciferase assays identified that STAT3 is a target gene of miR-124 in esophageal cancer cells. Over-expression of miR-124 significantly down-regulated the mRNA and protein levels of STAT3. Moreover, we found that the expression of miR-124 was consistently suppressed in esophageal cancer tissues and cell lines. Next, functional experiments showed that ectopic expression of miR-124 in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, and suppression of cell invasion in vitro, as well as inhibition of tumor growth in vivo. Moreover, restored the expression of STAT3 in esophageal cancer cells transfected with miR-124 before, could partially abolished the suppressive effects of miR-124 on the proliferation and invasion of Eca109 cells.


CONCLUSIONS
Collectively, these data suggest that miR-124 functions as a tumor suppressor in esophageal cancer through, at least partially, targeting STAT3 signaling pathway.
Department of Digestive Diseases, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China. chengyan_doc@126.com.
Yan
Y
Cheng
Department of Otolaryngology-head and neck surgery, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China. liyang_sam@163.com.
Yang
Y
Li
Department of Digestive Diseases, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China. dr_nianyuanyuan@126.com.
Yuanyuan
Y
Nian
Department of Digestive Diseases, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China. dongliu_doc@126.com.
Dong
D
Liu
Department of Digestive Diseases, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China. dr_daifei@126.com.
Fei
F
Dai
Department of Digestive Diseases, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China. dr_zhangjun01@126.com.
Jun
J
Zhang
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
D020413:3' Untranslated Regions; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor