ZBTB7/miR-137 Autoregulatory Circuit Promotes the Progression of Renal Carcinoma

Oncol Res. 2019 Sep 23;27(9):1007-1014. doi: 10.3727/096504018X15231148037228. Epub 2018 Apr 19.

Abstract

Renal carcinoma greatly threatens human health, but the involved molecular mechanisms are far from complete understanding. As a master oncogene driving the initiation of many other cancers, ZBTB7 has not been established to be associated with renal cancer. Our data revealed that ZBTB7 is highly expressed in renal carcinoma specimens and cell lines, compared with normal cells. The silencing of ZBTB7 suppressed the proliferation and invasion of renal cancer cells. ZBTB7 overexpression rendered normal cells with higher proliferation rates and invasiveness. An animal study further confirmed the role of ZBTB7 in the growth of renal carcinoma. Moreover, miR-137 was identified to negatively regulate the expression of ZBTB7, and its abundance is inversely correlated with that of ZBTB7 in renal carcinoma specimens and cell lines. ZBTB7 overexpression may be induced by miR-137 downregulation. Interestingly, ZBTB7 can also suppress miR-137 expression by binding to its recognition site within the miR-137 promoter region. Taken together, we identified an autoregulatory loop consisting of ZBTB7 and miR-137 in gastric cancers, and targeting this pathway may be an effective strategy for renal carcinoma cancer therapy.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease Progression
  • Down-Regulation
  • Heterografts
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • DNA-Binding Proteins
  • MIRN137 microRNA, human
  • MicroRNAs
  • Transcription Factors
  • ZBTB7A protein, human