Long noncoding RNA BX357664 regulates cell proliferation and epithelial-to-mesenchymal transition via inhibition of TGF-β1/p38/HSP27 signaling in renal cell carcinoma

Oncotarget. 2016 Dec 6;7(49):81410-81422. doi: 10.18632/oncotarget.12937.

Abstract

Antisense long noncoding RNAs (lncRNAs) are reported to play a regulating role in carcinogenesis of various human malignancies. However, the function of lncRNAs and their underlying mechanism in renal cell carcinoma (RCC) is still unknown. The aims of this study are to investigate the expression of lncRNA BX357664 in RCC and to explore its function in RCC cell lines. As a result, BX357664 was downregulated in RCC according to previous microarray analysis and qualitative real-time polymerase chain reaction. After the upregulation of BX357664, reduced migration, invasion, and proliferation capabilities in RCC cells were detected. Furthermore, Western blot analysis was conducted to identify the influence of BX357664 on epithelial-to-mesenchymal transition, matrix metalloproteinase 2, matrix metalloproteinase 9, and transforming growth factor-beta 1 (TGF-β1)/p38/HSP27 signaling pathway in RCC. Subsequently, upregulating the protein level of TGF-β1 in the presence of BX357664 could rescue the suppression of the malignant behavior mediated by BX357664, indicating that BX357664 attributed its inhibitory role to the suppression of TGF-β1. Therefore, we investigated a novel lncRNA BX357664, which might exhibit its inhibitory role in RCC metastasis and progression by blocking the TGF-β1/p38/HSP27 pathway.

Keywords: TGF-beta 1/p38/HSP27 signaling; epithelial-to-mesenchymal transition; lncRNA BX357664; long noncoding RNA (LncRNA); renal cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation* / drug effects
  • Epithelial-Mesenchymal Transition* / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • HSP27 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Molecular Chaperones
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction* / drug effects
  • Time Factors
  • Transfection
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • RNA, Long Noncoding
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • p38 Mitogen-Activated Protein Kinases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9