MicroRNA-98 promotes drug resistance and regulates mitochondrial dynamics by targeting LASS2 in bladder cancer cells

Exp Cell Res. 2018 Dec 15;373(1-2):188-197. doi: 10.1016/j.yexcr.2018.10.013. Epub 2018 Oct 25.


MicroRNA-98(miR-98) has been shown to be critical for tumorigenesis, however its involvement in bladder cancer are unclear. The present study aims to investigate the expression, biological roles and potential mechanisms of miR-98 in human bladder cancer. We found that miR-98 was upregulated in bladder urothelial carcinoma tissues compared with adjacent normal tissues. In addition, miR-98 expression was higher in bladder cancer cell lines than in uroepithelial cell line SV-HUC-1. Functional studies revealed that miR-98 mimic promoted proliferation of T24 cells while miR-98 inhibitor inhibited proliferation of BIU-87 cells. Moreover, miR-98 mimic increased cisplatin/doxorubicin resistance and inhibited apoptosis in T24 cells, while miR-98 inhibitor decreased chemoresistance and facilitated apoptosis in BIU-87 cells. Further experiments using MitoTracker and JC-1 staining showed that miR-98 could regulate mitochondrial fission/fusion balance and mitochondrial membrane potential. Western blot showed that miR-98 upregulated cyclin D1, p-Drp1 and Drp1. Using luciferase reporter assay, we demonstrated that LASS2 acted as a direct target of miR-98. LASS2 overexpression induced mitochondrial fusion and downregulated mitochondrial potential, with decreased p-Drp1 status. Additionally, LASS2 siRNA abrogated the effects of miR-98 mimic on Drp1phosphorylation and chemoresistance. We also found a negative correlation between LASS2 and miR-98 in bladder cancer tissues. In conclusion, our study demonstrates that miR-98 targets LASS2 and regulates bladder cancer chemoresistance through modulation of mitochondrial function.

Keywords: Bladder cancer; Chemoresistance; LASS2; Mitochondria; Proliferation; miR-98.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm*
  • Dynamins
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Potential, Mitochondrial
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / biosynthesis
  • MicroRNAs / physiology*
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria
  • Mitochondrial Dynamics*
  • Mitochondrial Proteins / metabolism
  • Sphingosine N-Acyltransferase / genetics*
  • Sphingosine N-Acyltransferase / metabolism
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / physiopathology


  • MIRN98 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Tumor Suppressor Proteins
  • CERS2 protein, human
  • Sphingosine N-Acyltransferase
  • GTP Phosphohydrolases
  • DNM1L protein, human
  • Dynamins