Pseudogene HSPB1P1 contributes to renal cell carcinoma proliferation and metastasis by targeting miR-296-5p to regulate HMGA1 expression

Cell Biol Int. 2021 Dec;45(12):2479-2489. doi: 10.1002/cbin.11694. Epub 2021 Sep 1.

Abstract

With the aid of next-generation sequencing technology, pseudogenes have been widely recognized as functional regulators in the development and progression of certain diseases, especially cancer. Our present study aimed to investigate the functions and molecular mechanisms of HSPB1-associated protein 1 pseudogene 1 (HSPB1P1) in renal cell carcinoma (RCC). HSPB1P1 expression at the mRNA levels was determined by quantitative real-time polymerase chain reaction, and its clinical significance was assessed. Cell viability was detected by Cell Counting Kit-8 assay. Cell migration and invasion were detected by transwell assays. The location of HSPB1P1 in RCC cells was detected by subcellular distribution analysis. The direct relationship between HSPB1P1 and miR-296-5p/HMGA1 axis was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Our results identify the elevated expression of HSPB1P1 in RCC tissues and cell lines, which predicted advanced progression and poor prognosis in patients with RCC. Knockdown of HSPB1P1 suppressed cell proliferation, migration, and invasion, and reversed epithelial-mesenchymal transition process in RCC. HSPB1P1 was mostly enriched in the cytoplasm and functioned as a miRNA sponge for miR-296-5p and then regulated high-mobility group A1 expression. In conclusion, our study indicated that HSPB1P1 contributed to RCC progression by targeting the miR-296-5p/HMGA1 axis, and should be considered as a promising biomarker and therapeutic target for clinical applications.

Keywords: HMGA1; HSPB1P1; metastasis; miRNA-296-5p; pseudogene; renal cell carcinoma.

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • HMGA1a Protein / genetics*
  • Heat-Shock Proteins / genetics*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • MicroRNAs / genetics*
  • Molecular Chaperones / genetics*
  • Prognosis
  • Pseudogenes / genetics*
  • Transcription Factors / genetics

Substances

  • HMGA1 protein, human
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • MIRN296 microRNA, human
  • MicroRNAs
  • Molecular Chaperones
  • Transcription Factors
  • HMGA1a Protein