LncRNA LINC00355 promotes EMT and metastasis of bladder cancer cells through the miR-424-5p/HMGA2 axis

Neoplasma. 2021 Nov;68(6):1225-1235. doi: 10.4149/neo_2021_210427N574. Epub 2021 Oct 10.

Abstract

Bladder cancer is a common malignant tumor with a high recurrence rate and mortality, while the detailed mechanisms for bladder cancer progression and metastasis are unknown. Recently, long non-coding RNAs (lncRNAs) have been reported to be involved in the development of cancers. In this study, we aim to investigate the role of lncRNA LINC00355 in bladder cancer progression and metastasis. The association between LINC00355 and the prognosis of bladder cancer patients was determined by Kaplan-Meier survival analysis. Cell migration and invasion ability were detected using the Transwell migration and invasion assay. The relationships of LINC00355, miR-424-5p, and High Mobility Group AT-Hook 2 (HMGA2) were verified through the luciferase assay and RNA pull-down assay. Xenograft tumor was established to evaluate tumor lung metastasis in vivo. qRT-PCR and western blot were used to detect gene expression. LINC00355 was upregulated in bladder cancer patients, especially in patients with higher TNM stage. Elevated LINC00355 was correlated with the poor prognosis of bladder cancer patients. Besides, overexpressed LINC00355 promoted migration, invasion, and epithelial-mesenchymal transition (EMT) ability of bladder cancer cells. Contrarily, decreased LINC00355 suppressed migration, invasion, and EMT ability of bladder cancer cells, and lung metastasis of xenograft tumors. Furthermore, LINC00355 could regulate HMGA2 expression by acting as a sponge for miR-424-5p. Overexpression of HMGA2 induced EMT of bladder cancer cells. Additionally, LINC00355 regulated the migration, invasion, and EMT ability of bladder cancer cells through modulating HMGA2 expression via sponging miR-424-5p. LINC00355 promoted migration, invasion, and EMT ability of bladder cancer through elevating HMGA2 expression via acting as a sponge for miR-424-5p.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic
  • HMGA2 Protein / genetics*
  • Humans
  • MicroRNAs* / genetics
  • Neoplasm Metastasis / genetics*
  • RNA, Long Noncoding* / genetics
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / pathology

Substances

  • HMGA2 Protein
  • HMGA2 protein, human
  • MIRN424 microrna, human
  • MicroRNAs
  • RNA, Long Noncoding