THAP7-AS1 orchestrates IGF2BP3-m6A-dependent CCN2 mRNA stabilization to promote lymphatic metastasis in bladder

Qiuyan Li1,2, Junjie Bai1,2, Shiwen Zheng3

  • 1Shengli Clinical College of Fujian Medical University Fuzhou 350001, Fujian, P. R. China.

Insights

THAP7-AS1, a long noncoding RNA, promotes bladder cancer spread to lymph nodes by stabilizing CCN2 mRNA. This pathway highlights THAP7-AS1 as a potential therapeutic target for muscle-invasive bladder cancer (MIBC).

Area of Science:

  • Molecular Biology
  • Oncology
  • RNA Biology

Background:

  • Lymphatic metastasis is a key factor in muscle-invasive bladder cancer (MIBC) treatment failure.
  • The specific RNA mechanisms driving lymphatic spread in bladder cancer are not fully understood.

Purpose of the Study:

  • To identify novel RNA regulators involved in bladder cancer lymphatic metastasis.
  • To elucidate the molecular mechanisms by which THAP7-AS1 influences bladder cancer progression.

Main Methods:

  • Identification and characterization of THAP7-AS1 in bladder cancer tissues.
  • In vitro assays for cell invasion and transendothelial migration.
  • In vivo studies of lymph node metastasis.
  • RNA immunoprecipitation and Western blot analyses to investigate molecular interactions.

Main Results:

  • THAP7-AS1 is upregulated in lymph node metastatic bladder cancer and linked to poor outcomes.
  • THAP7-AS1 enhances bladder cancer cell invasion, migration, and lymph node metastasis.
  • THAP7-AS1 interacts with IGF2BP3 to stabilize CCN2 mRNA, increasing CCN2 protein levels.

Conclusions:

  • A novel THAP7-AS1-IGF2BP3-m6A-CCN2 pathway promotes lymphatic metastasis in bladder cancer.
  • THAP7-AS1 is a potential biomarker and therapeutic target for bladder cancer (BCa).