STAT3 is involved in miR-124-mediated suppressive effects on esophageal cancer cells
Authors: Yuanyuan Nian
Dong Liu
Yang Li
Fei Dai
Yan Cheng
Jun Zhang
Journal: BMC Cancer (2015)
Discipline: CLINICAL MEDICINE
Keywords: Esophageal cancer; STAT3 signaling pathway; microRNAs; miR-124; gene expression regulation
Affiliations: Department of Digestive Diseases, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China. ., Department of Otolaryngology-head and neck surgery, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China. .

Abstract:  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. Conclusion: Collectively, these data suggest that miR-124 functions as a tumor suppressor in esophageal cancer through, at least partially, targeting STAT3 signaling pathway. 

Retracted: No

PubPeer comments:
 This paper has exact same style as another Chinese papers: A dual PI3K AKT mTOR signaling inhibitor miR-99a suppresses endometrial carcinoma American journal of translational research (2016) - 3 Comments pubmed: 27158364 issn: 1943-8141 , 
 Figure 2D. Surprisingly many cells feature in both the Scramble Eca109 and miR-124 TE-1 conditions. Most noticeable in the upper-right quadrants, enlarged here at right. ![file] , 
 #2 Yes, I found more than 6 similar papers with the exact same frame structure but the dots were intentionally added and modified. , 
 Those forgery are really hard to be spotted and their forgery ideas are super advanced. , 
 Don t announce how you spotted this particular sub-genre, or the true authors will know what *not* to do in future. , 
 #5 Got it. 5 more papers have been found with image duplication in another batch. , 
 #1 *[left]* Figure 3C.  MiR-124 suppresses esophageal cancer cell growth. ...(C, D) The influences of miR-124 on cell apoptosis and cell cycle progression were analyzed using fluorescence-activated cell sorting (FACS) . *[right]* Figure 2C from [Li et al (2016)] .  MiR-99a inhibits proliferation and invasion of EC cells. ... C, D. The influences of miR-99a on cell cycle distribution and apoptosis of HEC-1B and ishikawa cells were analyzed using fluorescence-activated cell sorting (FACS) . ![file] ,