Silencing of circular RNA PUM1 inhibits clear cell renal cell carcinoma progression through the miR-340-5p/FABP7 axis

J Recept Signal Transduct Res. 2022 Apr;42(2):141-150. doi: 10.1080/10799893.2020.1870494. Epub 2021 Jan 20.

Abstract

Circular RNAs (circRNAs) monitor the development of clear cell renal cell carcinoma (ccRCC). However, the role of CircPUM1 in ccRCC malignancy is not studied. We estimated the mechanism of CircPUM1 in ccRCC progression in this study. CircPUM1 expression in ccRCC tissues and cells was detected. The expression of CircPUM1 was interfered in ccRCC cells, and its effects on the growth of ccRCC cells were studied. Nuclear/cytosol fractionation assay was performed for the location of CircPUM1, and the downstream miR, gene, and pathway involved in ccRCC progression were explored through gain- and loss-of-function experiments. CircPUM1 was highly expressed in ccRCC samples and cells. Inhibition of CircPUM1 prevented the growth ccRCC cells. CircPUM1 was localized in the cytoplasm and bound to miR-340-5p. Overexpression of miR-340-5p inhibited the growth of ccRCC cells. miR-340-5p targeted FABP7, and CircPUM1 induced FABP7 expression and the activation of MEK/ERK pathway through competitively binding to miR-340-5p. Overexpression of FABP7 attenuated the inhibitory effect of CircPUM1 silencing on the growth of ccRCC cells. Overall, CircPUM1 upregulates FABP7 expression by competitively binding to miR-340-5p, and then activates the MEK/ERK pathway, thus promoting ccRCC progression.

Keywords: CircPUM1; Clear cell renal cell carcinoma; FABP7; MEK/ERK; miR-340-5p.

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Fatty Acid-Binding Protein 7* / genetics
  • Fatty Acid-Binding Protein 7* / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • RNA, Circular* / genetics
  • RNA-Binding Proteins / genetics
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • FABP7 protein, human
  • Fatty Acid-Binding Protein 7
  • MIRN340 microRNA, human
  • MicroRNAs
  • PUM1 protein, human
  • RNA, Circular
  • RNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Mitogen-Activated Protein Kinase Kinases