title: MiR-340 impedes the progression of laryngeal squamous cell carcinoma by targeting EZH2.
abstract: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the otolaryngeal region and accounts for 1-2% of all malignancies diagnosed worldwide. miR-340 down-regulation and EZH2 up-regulation have been frequently identified in multiple cancers, but the role of miR-340 and EZH2 in LSCC has not been explored. In this study, we investigated the regulative role of miR-340 in EZH2 expression and LSCC progression. The results showed that EZH2 was up-regulated and miR-340 was down-regulated in both Hep-2 cells and LSCC tissues. Molecularly, our results confirmed that miR-340 directly targeted EZH2 gene and inhibited EZH2 expression. MTT assay and BrdU assay showed that miR-340 transfection reduced the cell proliferation ability of Hep-2 cells. The transwell assay indicated that the invasion and migration ability of Hep-2 cells was dramatically inhibited by miR-340 transfection. In addition, miR-340 transfection induced cell apoptosis with concomitant enhancement of Bax, increase of Caspase-3 expression and activity, and reduction of Bcl-2 expression in Hep-2 cells. Both miR-340 transfection and EZH2 knockdown induced p27 expression and suppressed PI3K/Akt activation in Hep-2 cells. Strikingly, EZH2 knockdown reduced cell proliferation, and EZH2 overexpression significantly rescued the miR-340-mediated suppressive effect on cell proliferation. Moreover, miR-340 could obviously induce the inhibition of Hep-2 cell-derived tumor growth and EZH2/p27 expression ratio in vivo. Taken together, these data suggest that miR-340 impedes LSCC progression by targeting EZH2 with the possible mechanism to enhance the expression of anti-oncogene p27 and suppress PI3K/Akt activation, providing a novel target and a potential therapeutic pathway against LSCC.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, PR China.
authors.forename: Wenfa
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, PR China.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, PR China.
authors.forename: Baocai
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, PR China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Lian
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: C570046:MIRN340 microRNA, human; D035683:MicroRNAs; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: EZH2; LSCC; Progression; miR-340; p27