title: MicroRNA-93 regulates cyclin G2 expression and plays an oncogenic role in laryngeal squamous cell carcinoma.
abstract: microRNA93 (miR-93) is expressed in the miR‑106b-25 cluster, located in intron 13 of the MCM7 gene. Our previous study found that miR-93 was significantly upregulated in laryngeal squamous cell carcinoma (LSCC), and cyclin G2 (CCNG2) was a potential target of miR-93 in LSCC. However, the possible functions and molecular mechanisms of miR-93 in LSCC remain unknown. In the present study, we show that the level of CCNG2 protein expression was significantly lower in LSCC cancer tissue than normal tissues. The level of CCNG2 was correlated with clinical stages, lymph node metastasis and histological grade. We further show that the expression level of miR-93 was inversely correlated with CCNG2 expression in clinical specimens. Furthermore, gain-of-function assays revealed that miR-93 promoted cell proliferation, decreased apoptosis rates, induced cell cycle arrest and promoted cell migration and invasion, whereas silencing of miR-93 attenuated these carcinogenic processes. In addition, overexpression of miR-93 in Hep-2 cells could reduce the mRNA and protein levels of CCNG2, whereas silencing of miR-93 in Hep-2 cells significantly increased CCNG2 expression. A luciferase assay verified that miR-93 could bind to the 3' untranslated region of CCNG2. Importantly, ectopic expression of CCNG2 in miR-93 cells rescued the effect of miR-93 on LSCC proliferation. Knockdown of CCNG2 promoted cell proliferation resembling that of miR-93 overexpression. These findings demonstrated that miR-93 promotes tumor growth by directly suppressing CCNG2. Taken together, these results suggested that this newly identified miR-93-CCNG2 axis may be involved in LSCC proliferation and progression. Our findings provide novel potential targets for LSCC therapy and prognosis.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Fudan University Affiliated Eye, Ear, Nose and Throat Hospital, Shanghai 200031, P.R. China.
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Fudan University Affiliated Eye, Ear, Nose and Throat Hospital, Shanghai 200031, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Fudan University Affiliated Eye, Ear, Nose and Throat Hospital, Shanghai 200031, P.R. China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Fudan University Affiliated Eye, Ear, Nose and Throat Hospital, Shanghai 200031, P.R. China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Gong
authors.affiliation: Central Laboratory, Fudan University Affiliated Eye, Ear, Nose and Throat Hospital, Shanghai 200031, P.R. China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D056767:Cyclin G2 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009857:Oncogenes; D014407:Tumor Cells, Cultured
chemical_list: C101593:CCNG2 protein, human; D056767:Cyclin G2; C543350:MIRN93 microRNA, human; D035683:MicroRNAs