Song Yang1, Xiangyi Li2, Wenhao Shen1, Haitao Hu3, Chen Li4, Gaohua Han5. 1. Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, China. 2. Department of Endocrinology, Taizhou People's Hospital, Taizhou, Jiangsu, China. 3. Clinical Laboratory, Taizhou People's Hospital, Taizhou, Jiangsu, China. 4. Department of Stomatology, Taizhou People's Hospital, Taizhou, Jiangsu, China. 5. Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, China. Electronic address: ngmieqiongbbxpr@163.com.
Abstract
BACKGROUND: MicroRNAs have been reported to play regulatory functions in various cancers, including esophageal cancer. The aim of this study was to investigate the effects of miR-140 on the progression of esophageal cancer and the underlying regulatory mechanism. METHODS: The levels of miR-140 and zinc finger E-box-binding homeobox 2 (ZEB2) messenger RNA in esophageal cancer tissues and cell lines were measured by quantitative real-time polymerase chain reaction. The protein levels of ZEB2, β-catenin, c-Myc, and cyclinD1 were determined by Western blot. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, the relationship between miR-140 and ZEB2 was predicted by TargetScan online database and confirmed by dual-luciferase reporter assay. The tumor xenograft model was used to verify the role of miR-140 in esophageal cancer progression in vivo. RESULTS: The expression of miR-140 was downregulated whereas ZEB2 expression was upregulated in esophageal cancer tissues compared with paracancerous normal tissues. Functionally, both miR-140 overexpression and ZEB2 knockdown inhibited proliferation, migration, and invasion and induced apoptosis in esophageal cancer cells. ZEB2 overexpression reversed the effects of miR-140 on proliferation, apoptosis, migration, and invasion of esophageal cancer cells. Mechanistically, ZEB2 was identified as a target of miR-140. Furthermore, miR-140 suppressed Wnt/β-catenin pathway by regulating ZEB2 expression in esophageal cancer cells. MiR-140 inhibited tumor growth of esophageal cancer through repressing ZEB2 expression in vivo. CONCLUSIONS: Our results demonstrated that miR-140 inhibited esophageal cancer development by targeting ZEB2 through inactivating Wnt/β-catenin pathway.
BACKGROUND: MicroRNAs have been reported to play regulatory functions in various cancers, including esophageal cancer. The aim of this study was to investigate the effects of miR-140 on the progression of esophageal cancer and the underlying regulatory mechanism. METHODS: The levels of miR-140 and zinc finger E-box-binding homeobox 2 (ZEB2) messenger RNA in esophageal cancer tissues and cell lines were measured by quantitative real-time polymerase chain reaction. The protein levels of ZEB2, β-catenin, c-Myc, and cyclinD1 were determined by Western blot. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, the relationship between miR-140 and ZEB2 was predicted by TargetScan online database and confirmed by dual-luciferase reporter assay. The tumor xenograft model was used to verify the role of miR-140 in esophageal cancer progression in vivo. RESULTS: The expression of miR-140 was downregulated whereas ZEB2 expression was upregulated in esophageal cancer tissues compared with paracancerous normal tissues. Functionally, both miR-140 overexpression and ZEB2 knockdown inhibited proliferation, migration, and invasion and induced apoptosis in esophageal cancer cells. ZEB2 overexpression reversed the effects of miR-140 on proliferation, apoptosis, migration, and invasion of esophageal cancer cells. Mechanistically, ZEB2 was identified as a target of miR-140. Furthermore, miR-140 suppressed Wnt/β-catenin pathway by regulating ZEB2 expression in esophageal cancer cells. MiR-140 inhibited tumor growth of esophageal cancer through repressing ZEB2 expression in vivo. CONCLUSIONS: Our results demonstrated that miR-140 inhibited esophageal cancer development by targeting ZEB2 through inactivating Wnt/β-catenin pathway.
Authors: Eman A Toraih; Manal S Fawzy; Bo Ning; Mourad Zerfaoui; Youssef Errami; Emmanuelle M Ruiz; Mohammad H Hussein; Muhib Haidari; Melyssa Bratton; Giovane G Tortelote; Sylvia Hilliard; Naris Nilubol; Jonathon O Russell; Mohamed A Shama; Samir S El-Dahr; Krzysztof Moroz; Tony Hu; Emad Kandil Journal: Cancers (Basel) Date: 2022-08-26 Impact factor: 6.575