An angiogenesis‑related lncRNA signature for the prognostic prediction of patients with bladder cancer and LINC02321 promotes bladder cancer progression via the VEGFA signaling pathway

Mol Med Rep. 2023 Feb;27(2):38. doi: 10.3892/mmr.2022.12925. Epub 2022 Dec 29.

Abstract

The mechanism underlying bladder cancer metastasis is associated with tumor angiogenesis. The present study aimed to evaluate the predictive role and value of an angiogenesis‑associated long non‑coding (lnc)RNA signature in patients with bladder cancer and the role of long intergenic non‑coding RNA (LINC)02321 in the progression of this malignancy. Angiogenesis‑related lncRNAs were screened using Pearson correlation analysis and the signaturewas constructed using Cox regression analysis and evaluated using the receiver operating characteristic curve. LINC02321, which expressed the largest difference in bladder cancer, was screened using reverse transcription‑quantitative PCR. The role of LINC02321 in the malignant progression of bladder cancer was evaluated using Transwell, wound healing and Cell Counting Kit 8 assays. A total of six angiogenesis‑associated lncRNAs (USP30‑AS1, LINC02321, PSMB8‑AS1, KRT7‑AS, LINC01767 and OCIAD1‑AS1) were identified as candidates for the prognostic signature using Cox regression analysis. The overall survival of patients in the low‑risk group was significantly longer compared with that in the high‑risk group, with the highest area under the curve value being 0.807. A nomogram was constructed based on the traditional clinical indicators (age, sex, grade, American Joint Committee on Cancer stage) and risk score of patients. Compared with the traditional clinical indicators, the risk score demonstrated better clinical prediction capacity for predicting the prognosis of patients with bladder cancer. The Cancer Genome Atlas prediction and RT‑qPCR experimental results demonstrated that only LINC02321 was highly expressed in bladder cancer tissue and promoted the proliferation, invasion, migration and cisplatin resistance of the malignancy. Gene set enrichment, Pearson's correlation analysis and experimental results demonstrated that the VEGFA signalling pathway may be involved in the LINC02321‑regulated progression of bladder cancer. In conclusion, the six angiogenesis‑associated lncRNA signatures reported in the present study may be used to predict the prognosis of patients with bladder cancer, and LINC02321 promoted malignant progression of bladder cancer via the VEGFA signalling pathway.

Keywords: angiogenesis; bioinformatics; bladder cancer; long intergenic non‑coding RNA 02321; long non‑coding RNA signature.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mitochondrial Proteins / metabolism
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Risk Factors
  • Signal Transduction
  • Thiolester Hydrolases / genetics
  • Thiolester Hydrolases / metabolism
  • Urinary Bladder Neoplasms* / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • RNA, Long Noncoding
  • Biomarkers, Tumor
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Usp30 protein, human
  • Thiolester Hydrolases
  • Mitochondrial Proteins

Grants and funding

The present study was funded by Zhao Kang and Tao Li.