MAN1B1 is associated with poor prognosis and modulates proliferation and apoptosis in bladder cancer

Gene. 2018 Dec 30:679:314-319. doi: 10.1016/j.gene.2018.09.022. Epub 2018 Sep 12.

Abstract

Bladder cancer (BC) has been regarded as the most common malignancy of the urinary system worldwide. With lack of investigations for molecular pathogenesis underlying that develop BC, the therapeutic efficacy of several therapeutic approaches existing is still unsatisfactory. Here, our study aimed to explore the potentially biological function of MAN1B1 on BC. In this study, MAN1B1 expression level in BC tissues and normal tissues was analyzed based on The Cancer Genome Atlas (TCGA) data and correlation between its expression and prognosis was determined using Kaplan-Meier analysis. Knockout of MAN1B1 was performed using silencing RNA and the efficacy of MAN1B1 knockout was identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. The BC cells proliferation was assessed by Cell Counting Kit-8 (CCK8) assay, and then the cells apoptosis was detected by Annexin V-fluorescein isothiocyanate (Annexin V-FITC)/propidium iodide (PI) staining and flow cytometry following MAN1B1 knocked down by small interfering RNA. Protein kinase B (AKT) signaling was evaluated by detecting related markers, namely AKT, p-AKT, 4E-BP-1 and Bax using western blot assay. As a result, the MAN1B1 expression was higher in BC tissues than those in normal tissues, besides, its overexpression was associated with poor prognosis. Moreover, MAN1B1 reduction by silencing RNA approach resulted in BC cells proliferation suppression and BC cells apoptosis promotion. Finally, AKT signaling activity was inhibited by MAN1B1 silencing. Taken together, these results unraveled that MAN1B1 may act on an oncogenic action in BC, which improved the likelihood of MAN1B1 taking on a promising prognostic biomarker and a potential target for treating BC.

Keywords: Apoptosis; Bladder cancer; MAN1B1; Prognosis; Proliferation.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Genetic Association Studies
  • Humans
  • Kaplan-Meier Estimate
  • Mannosidases / genetics*
  • Mannosidases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Survival Analysis
  • Up-Regulation*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Mannosidases
  • mannosyl-oligosaccharide 1,2-alpha-mannosidase