期刊
ONCOTARGET
卷 7, 期 2, 页码 1777-1795出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6499
关键词
PLCE1; miR-145; esophageal carcinoma; proliferation; invasion
资金
- National Natural Science Foundation of China [81160301, 81360358, 81460362, 81560399, 81260301]
- Major science and technology projects of Shihezi University [gxjs2014-zdgg06]
- Ministry of Science and Technology of China [2012AA02A503]
- high-level talent project of Shihezi University [RCZX201533]
- jointly foundation for nurturing the outstanding young scientists of Shihezi University [2013ZRKXYQ-YD19]
- Doctor grant of Xinjiang Production and Construction Corps [2014BB019]
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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