MicroRNA-34a functions as a tumor suppressor by directly targeting oncogenic PLCE1 in Kazakh esophageal squamous cell carcinoma

// Xiao-Bin Cui 1, 2 , Hao Peng 1 , Ran-Ran Li 1 , Jian-Qin Mu 3 , Lan Yang 1 , Na Li 4 , Chun-Xia Liu 1 , Jian-Ming Hu 1 , Shu-Gang Li 1 , Yutao Wei 5 , Laibo-Yin 5 , Hong Zhou 6 , Feng Li 1, 2 and Yun-Zhao Chen 1, 7 1 Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China 2 Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China 3 First Department of Internal Medicine, Xinjiang Production and Construction Corp Hospital of Chinese People’s Armed Police Force, Urumqi, China 4 Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China 5 Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China 6 Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia 7 The People's Hospital of Suzhou National Hi-Tech District, Suzhou, China Correspondence to: Feng Li, email: lifeng7855@126.com Yun-Zhao Chen, email: cyz0515@sina.com Keywords: esophageal cancer, PLCE1, miR-34a, tumor suppressor, Kazakh Received: December 27, 2016      Accepted: July 18, 2017      Published: September 27, 2017 ABSTRACT 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.