Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma
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Xiao-Bin Cui1,2,*, Su Li1,3,*, Ting-Ting Li1,*, Hao Peng1, Ting-Ting Jin1, Shu-Mao Zhang1, Chun-Xia Liu1, Lan Yang1, Yao-Yuan Shen4, Shu-Gang Li1, Na Li5, Yong Li6, Jian-Ming Hu1, Jin-Fang Jiang1, Jing Suo1, Yan Qi1, Wei-Hua Liang1, Liang-Hai Wang1, Hong-Wei Dang1, Li Li1, Wei-Wei Cao7, Yutao Wei8, Laibo-Yin8, Chuan-Yue Wu1,9, Xiang-Lin Yuan2, Hong Zhou10, Yu Zheng10, Yun-Zhao Chen1, Feng Li1,2
1Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China
2Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
3Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang, China
4Department of Pathology, People Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
5Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China
6Department of CT and MRI, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China
7The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China
8Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China
9Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
10Bone Research Program, ANZAC Research Institute, University of Sydney, New South Wales, Australia
*These authors contributed equally to this work
Feng Li, e-mail: firstname.lastname@example.org
Yunzhao Chen, e-mail: email@example.com
Keywords: PLCE1, miR-145, esophageal carcinoma, proliferation, invasion
Received: October 23, 2015 Accepted: October 29, 2015 Published: December 08, 2015
Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in esophageal squamous cell carcinoma (ESCC). Nevertheless, the role of PLCE1 in ESCC tumorigenesis has not been elucidated. In this study, we determined the function of PLCE1 and its regulatory microRNA (miRNA) in ESCC. PLCE1 protein was excessively expressed in ESCC and precancerous lesions compared with that in normal tissues. High PLCE1 expression levels in ESCC were significantly linked with poor overall survival. Knockdown of PLCE1 promoted the apoptosis, cytokine-induced apoptosis, and sensitivity of cancer cells to chemotherapeutic drugs but abrogated the proliferation and EMT phenotype of ESCC in vitro. Notably, miR-145 was newly identified as a potent repressor of PLCE1 expression by directly targeting the 3′UTR of PLCE1. MiR-145 also inhibited cell proliferation, migration, and metastasis, as well as controlled the cytoskeleton dynamics of esophageal cancer. Moreover, miR-145 was expressed at low levels in a large cohort of patients with ESCC and was inversely correlated with PLCE1 protein expression in cancer cells and tissues. These findings demonstrate that PLCE1 functions as tumor promoter in ESCC and can be suppressed by miR-145 through inhibition of PLCE1 translation. Hence, delivery of PLCE1-targeting miR-145 is a potential therapeutic approach for esophageal cancer.
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