title: Knockdown of zinc transporter ZIP5 (SLC39A5) expression significantly inhibits human esophageal cancer progression.
abstract: ZIP5 is a central player in mammalian zinc metabolism. Studies suggest that ZIP5 is differentially expressed during esophageal tumorigenesis, yet the role of ZIP5 in esophageal cancer cells has not yet been clarified. Immunohistochemistry, western blotting and qRT-PCR techniques were used to detect ZIP5 expression in esophageal squamous cell carcinoma (ESCC) tissues. We established a stable knockdown ZIP5 cell line (KYSE170K) derived from the ESCC cell line KYSE170. We conducted MTT and CCK-8 assays to determine the role of ZIP5 in cell proliferation, Transwell assays to detect migration and invasion, and flow cytometry (FCM) to detect apoptosis and cell cycle percentage using KYSE170K cells. We conducted a gene profiling study to detect the expression of genes related to tumor progression. The results demonstrated that ZIP5 protein and mRNA expression was highest in ESCC, intermediate in para-carcinoma and lowest in normal tissue. ZIP5 knockdown decreased proliferation by 28 and 38%, respectively, according to the MTT and CCK-8 assays. Migration and invasion decreased by 54 and 68%, respectively, according to the Transwell assays. COX2 expression was decreased by 68 and 75% at the mRNA and protein level, respectively, and cyclin D1 mRNA and protein expression was decreased following 62 and 60%, respectively, by knockdown of ZIP5, which upregulated the mRNA and protein expression of E-cadherin by 80 and 60%, respectively. ZIP5 knockdown inhibited the proliferation, migration and invasion of ESCC and suppressed COX2, cyclin D1 and E-cadherin expression, which led to the inhibition of cell progression in ESCC.
authors.affiliation: Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Jianghui
authors.initials: J
authors.lastname: Liu
authors.affiliation: Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Yutong
authors.initials: Y
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D012333:RNA, Messenger
chemical_list: C530104:CCND1 protein, human; D015820:Cadherins; D027682:Cation Transport Proteins; D012333:RNA, Messenger; C521171:SLC39A5 protein, human; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human