title: METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion.
abstract: The incidence of bladder cancer has increased in the last few decades, thus novel markers for early diagnosis and more efficacious treatment are urgently needed. It found that METTTL13 protein is aberrant expression in variety of human cancers and METTL13 was involved in oncogenic pathways. However, the role of METTL13 has been unexplored in bladder cancer to date. Here, expression of METTL13 was lower in bladder cancer tissue samples and cancer cell lines than in normal bladder tissue and cell lines. METTL13 was downregulated in the late stages of the disease and was maintained at low level throughout the tumor progression process based on tumor node metastasis (TNM) staging. Further research suggested that METTL13 negatively regulates cell proliferation in bladder cancer and reinstates G1/S checkpoint via the coordinated downregulation of CDK6, CDK4 and CCND1, decreased phosphorylation of Rb and subsequent delayed cell cycle progression. Moreover, METTL13-dependent inhibition of bladder cancer cell migration and invasion is mediated by downregulation of FAK (Focal adhesion kinase) phosphorylation, AKT (v-akt murine thymoma viral oncogene) phosphorylation, β-catenin expression and MMP-9 expression. These integrated efforts have identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention.
authors.affiliation: Department of Urology, the First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Shengjing Hospital of China Medical University, Shenyang City, 110022, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urology, the First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Chuize
authors.initials: C
authors.lastname: Kong
authors.affiliation: Department of Urology, the First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhan
authors.affiliation: Department of Urology, the First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Urology, the First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Man
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D015815:Cell Adhesion Molecules; C583021:EEF1AKNMT protein, human; D008780:Methyltransferases