miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer

Tumour Biol. 2015 Dec;36(12):9631-40. doi: 10.1007/s13277-015-3713-7. Epub 2015 Jul 7.


MicroRNA-9 upregulation was reported in several tumors. However, its function and mechanism in human bladder cancer remains obscure. The present study aims to identify the expression pattern, biological roles and potential mechanism of miR-9 in human bladder cancers. We found that expression level of miR-9 in bladder cancer tissues was higher than normal tissues. miR-9 mimic transfection was performed in T24 and 5637 cells with low miR-9 expression, and miR-9 inhibitor was employed in BIU-87 cell line with high endogenous expression. miR-9 increased cell proliferation, cell cycle progression, invasion and chemoresistance, with upregulation of cyclin D1, MMP9, Bcl-2, and survivin and downregulation of E-cadherin. Using luciferase reporter assay, we confirmed that LASS2 was a direct target of miR-9 in bladder cancer cells. Transfection of miR-9 mimic downregulated LASS2 expression. LASS2 transfection downregulated Bcl-2 and survivin expression, which were induced by miR-9 mimic in both cell lines. In conclusion, these results indicate that miR-9 upregulation might be associated with malignant phenotype of bladder cancer. miR-9 promotes chemoresistance of bladder cancer cells by target LASS2.

Keywords: Bladder cancer; Chemoresistance; LASS2; miR-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Proteins / biosynthesis
  • Sphingosine N-Acyltransferase / biosynthesis*
  • Sphingosine N-Acyltransferase / genetics
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology


  • MIRN92 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • CERS2 protein, human
  • Sphingosine N-Acyltransferase