title: Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.|Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Cui
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.|Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang, China.
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Jin
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Shu-Mao
authors.initials: SM
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Liu
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology, People Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
authors.forename: Yao-Yuan
authors.initials: YY
authors.lastname: Shen
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Shu-Gang
authors.initials: SG
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of CT and MRI, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Hu
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Suo
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Liang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Liang-Hai
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Dang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Cao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China.
authors.lastname: Laibo-Yin
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.|Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Chuan-Yue
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiang-Lin
authors.initials: XL
authors.lastname: Yuan
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, New South Wales, Australia.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, New South Wales, Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
authors.forename: Yun-Zhao
authors.initials: YZ
authors.lastname: Chen
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.|Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D018613:Microscopy, Confocal; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D054801:Phosphoinositide Phospholipase C / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon
keywords: PLCE1; esophageal carcinoma; invasion; miR-145; proliferation