miR-302b is a potential molecular marker of esophageal squamous cell carcinoma and functions as a tumor suppressor by targeting ErbB4.
BACKGROUND
ErbB4 expression has been noted in various tumors, but its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate whether miR-302b regulates the expression of ErbB4 at the post-transcriptional level and to determine its expression, significance, and function in ESCC.


METHODS
We used real-time reverse transcriptase-polymerase chain reaction to quantify the expression of miR-302b in 50 ESCC tissues and analyzed its relationship with clinicopathological factors and survival. Then, we investigated the post-transcriptional regulation of ErbB4 expression using immunoblot analysis and luciferase reporter assays. Finally, the effects of miR-302b on proliferation, apoptosis, and invasion of ESCC cells was detected using MTT, flow cytometric analysis, and transwell invasion assays, respectively.


RESULTS
miR-302b was significantly down-regulated and correlated with tumor differentiation and lymph node metastasis in ESCC. Univariate and multivariate analyses indicated that low miR-302b expression might be a poor prognostic factor. Further studies demonstrated that miR-302b post-transcriptionally down-regulated the expression of ErbB4 in vitro. Moreover, miR-302b inhibited proliferation by inducing apoptosis and repressed invasion in the ESCC cell lines.


CONCLUSIONS
miR-302b is a potential molecular marker of ESCC and functions as a tumor suppressor by post-transcriptionally regulating ErbB4.
Mingxin
M
Zhang
Qi
Q
Yang
Lingmin
L
Zhang
Suna
S
Zhou
Wenguang
W
Ye
Qinglin
Q
Yao
Zongfang
Z
Li
Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038 Shaanxi Province, China. hchen@mail.xjtu.edu.cn.
Cheng
C
Huang
Qinsheng
Q
Wen
Jingjie
J
Wang
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002465:Cell Movement; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D066247:Receptor, ErbB-4; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins
C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4