MicroRNA-34a functions as a tumor suppressor by directly targeting oncogenic PLCE1 in Kazakh esophageal squamous cell carcinoma
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Xiao-Bin Cui1,2, Hao Peng1, Ran-Ran Li1, Jian-Qin Mu3, Lan Yang1, Na Li4, Chun-Xia Liu1, Jian-Ming Hu1, Shu-Gang Li1, Yutao Wei5, Laibo-Yin5, Hong Zhou6, Feng Li1,2 and Yun-Zhao Chen1,7
1Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China
2Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
3First Department of Internal Medicine, Xinjiang Production and Construction Corp Hospital of Chinese People’s Armed Police Force, Urumqi, China
4Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China
5Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China
6Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia
7The People's Hospital of Suzhou National Hi-Tech District, Suzhou, China
Feng Li, email: [email protected]
Yun-Zhao Chen, email: [email protected]
Keywords: esophageal cancer, PLCE1, miR-34a, tumor suppressor, Kazakh
Received: December 27, 2016 Accepted: July 18, 2017 Published: September 27, 2017
Esophageal squamous cell carcinoma (ESCC) is one of the frequent malignant tumors with poor prognosis worldwide. Identifying the prognostic biomarkers and potential mechanisms of such tumors has attracted increasing interest in esophageal cancer biology. Our previous study showed that phospholipase C elipson 1 (PLCE1) expression is up-regulated and associated with disease progression in esophageal carcinoma. MicroRNAs (miRNAs) play vital roles in regulating its target gene expression. However, studies on miRNA-regulated PLCE1 expression and its cellular function are still very few. We found that miR-34a is significantly expressed lower in ESCC tissues. We further showed that PLCE1 is a direct functional target gene of miR-34a, and the functional roles of miR-34a in ESCC cell lines in vitro were also determined through gain- and loss-of-function analyses. Results revealed that miR-34a functions as a tumor suppressor by inhibiting the proliferation, migration, and EMT phenotype, as well as promoting apoptosis of ESCC cell lines. Moreover, PLCE1 is overexpressed in ESCC tumors and promotes tumorigenicity in vivo and vitro. PLCE1 expression is negatively correlated with miR-34a profiles in ESCC tissues. Our data suggest that miR-34a exerts its anti-cancer function by suppressing PLCE1. The newly identified miR-34a/PLCE1 axis partially illustrates the molecular mechanism of ESCC metastasis and represents a new candidate therapeutic target for ESCC treatment.
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