Long noncoding RNA ZFPM2-AS1 regulates renal cell carcinoma progression via miR-130a-3p/ESCO2

Kaohsiung J Med Sci. 2022 Jun;38(6):530-541. doi: 10.1002/kjm2.12527. Epub 2022 Mar 8.

Abstract

Previous studies reported that long noncoding RNA (lncRNA) ZFPM2-AS1 is upregulated in renal cell carcinoma (RCC). However, the biological role of lncRNA ZFPM2-AS1 in RCC has not been explored. In this study, we investigated the role of lncRNA ZFPM2-AS1 in the progression of RCC. Quantitative real-time polymerase chain reaction was used for gene expression analysis, and functional assays including Cell Counting Kit-8 assay, flow cytometry-based apoptosis assay and transwell migration assays were performed to examine the malignant phenotypes. The functional interaction between ZFPM2-AS1 or miR-130A-3P and their targets was detected by dual-luciferase reporter assay. We found that the expressions of ZFPM2-AS1 and ESCO2 were upregulated in RCC tissues and cells, whereas miR-130a-3p was downregulated. The expression level of ZFPM2-AS1 is significantly associated with advanced TNM, distant metastasis, lymphatic metastasis, and a poor overall survival in RCC patients. Silencing ZFPM2-AS1 in RCC cells suppressed cell proliferation, invasion, and migration, and induced cell apoptosis. ZFPM2-AS1 interacted with miR-130A-3P and negatively regulated its expression in RCC cells. We further showed that ESCO2 was a downstream target of miR-130a-3p. Both miR-130a-3p inhibitor and ESCO2 overexpression could rescue the inhibitory effects of ZFPM2-AS1 knockdown in RCC cells. Together, our study demonstrates that ZFPM2-AS1 plays an oncogenic role in RCC progression via the miR-130a-3p/ESCO2 axis.

Keywords: ESCO2; RCC; ZFPM2-AS1; miR-130a-3p.

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Acetyltransferases / pharmacology
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / metabolism
  • Transcription Factors / genetics

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors
  • ZFPM2 protein, human
  • Acetyltransferases
  • ESCO2 protein, human