title: MiR-498 in esophageal squamous cell carcinoma: clinicopathological impacts and functional interactions.
abstract: MicroRNA-498 plays a crucial role in progression of many carcinomas. The signaling pathways by which miR-498 modulates carcinogenesis are still unknown. Also, miR-498-associated molecular pathogenesis has never been studied in esophageal squamous cell carcinoma (ESCC). Herein, we aimed to examine the expression and functional roles of miR-498 in ESCC as well as its influences on the clinicopathological features in patients with ESCC. Expression of miR-498 was investigated in 93 ESCC tissues and 5 ESCC cell lines using quantitative real-time polymerase chain reaction. In vitro effects of miR-498 on cellular process were studied followed by overexpression of miR-498. Western blot and immunofluorescence techniques were used to identify the interacting targets for miR-498 in ESCC. miR-498 expression was significantly reduced in ESCC when compared with the nonneoplastic esophageal tissues (P<.05). Patients with low miR-498 expression showed different histological grading of cancer and survival rates when compared with the patients with high miR-498 expression. Overexpression of miR-498 in ESCC cell lines induced remarkable reductions of cell proliferation, barrier penetration, and colony formation when compared with control and wild-type counterparts. Also, miR-498 activated the FOXO1/KLF6 transcriptional axis in ESCC. In addition, miR-498 overexpression increased p21 protein expression and led to reduced cancer cell growth. To conclude, reduced expression of miR-498 in ESCC and in vitro analysis have confirmed the tumor suppressor properties of miR-498 by modulating the FOXO1/KLF6 signaling pathway. The changes in miR-498 expression may have impacts on the clinical pathological parameters of ESCC as well as in the management of the patients with ESCC.
authors.affiliation: Cancer Molecular Pathology of School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, 4222, Australia; Department of Biochemistry and Molecular Biology, University of Rajshahi, 6205, Bangladesh.
authors.forename: Farhadul
authors.initials: F
authors.lastname: Islam
authors.affiliation: Cancer Molecular Pathology of School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, 4222, Australia; School of Medical Sciences, Griffith University, Gold Coast, 4222, Australia.
authors.forename: Vinod
authors.initials: V
authors.lastname: Gopalan
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital.
authors.forename: Simon
authors.initials: S
authors.lastname: Law
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, the Hong Kong Polytechnic University.
authors.forename: Johnny Cheuk-On
authors.initials: JC
authors.lastname: Tang
authors.affiliation: Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital.
authors.forename: Kwok-Wah
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Cancer Molecular Pathology of School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, 4222, Australia. Electronic address: a.lam@griffith.edu.au.
authors.forename: Alfred King-Yin
authors.initials: AK
authors.lastname: Lam
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005455:Fluorescent Antibody Technique; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D016019:Survival Analysis; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; C578093:MIRN498 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins
keywords: Esophageal; Grade; Squamous cell carcinoma; Survival; miR-498