Long non-coding RNA LINC00565 regulates ADAM19 expression through sponging microRNA-532-3p, thereby facilitating clear cell renal cell carcinoma progression

Chin J Physiol. 2023 Nov-Dec;66(6):474-484. doi: 10.4103/cjop.CJOP-D-23-00078.

Abstract

Proven by publications, long non-coding RNAs (lncRNAs) play critical roles in the development of clear cell renal cell carcinoma (ccRCC). Although lncRNA LINC00565 has been implicated in the progression of various cancers, its biological effects on ccRCC remain unknown. This study aimed to investigate the biological functions of LINC00565, as well as its potential mechanism in ccRCC. Here, the expression data of mature microRNAs (miRNAs) (normal: 71, tumor: 545), messenger RNAs (mRNAs), and lncRNAs (normal: 72, tumor: 539) of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database and subjected to differential expression analysis. Quantitative reverse transcriptase polymerase chain reaction analyzed the expression levels of LINC00565, miR-532-3p, and ADAM19 mRNA. TCGA database, dual-luciferase report detection, and Argonaute 2 RNA immunoprecipitation were utilized to confirm the relationships between LINC00565 and miR-532-3p and between miR-532-3p and ADAM19, respectively. The progression of ccRCC cells was determined via CCK-8, colony formation, scratch healing, and transwell assays. Western blot was applied to detect the protein levels of epithelial-mesenchymal transition markers and ADAM19. We herein suggested that LINC00565 was prominently upregulated in ccRCC tissues and cells. Knockdown of LINC00565 repressed cell progression. We further predicted and validated miR-532-3p as a target of LINC00565, and miR-532-3p could target ADAM19. Knockdown of LINC00565 resulted in ADAM19 level downregulation in ccRCC cells and suppressed miR-532-3p could restore ADAM19 level. Thus, the three RNAs constructed a ceRNA network. Overexpressed ADAM19 could eliminate the anticancer effects caused by knocking down LINC00565 on ccRCC cells. In conclusion, LINC00565 upregulated ADAM19 via absorbing miR-532-3p, thereby facilitating the progression of ccRCC cells.

Keywords: ADAM19; LINC00565; clear cell renal cell carcinoma; miR-532-3p.

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • ADAM19 protein, human
  • ADAM Proteins
  • MIRN532 microRNA, human