ROCK2-RNA interaction map reveals multiple biological mechanisms underlying tumor progression in renal cell carcinoma

Zhengdong Hong1, Xuexin Chen2, Lei Wang3,4

  • 1Department of Urology Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Human Cell
|July 7, 2023
PubMed

Insights

Rho-associated coiled-coil forming protein kinase 2 (ROCK2) plays a key role in kidney cancer. This study reveals ROCK2’s complex RNA interactions and their link to tumorigenic pathways in renal cell carcinoma (RCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Renal cell carcinoma (RCC) is the most common kidney cancer, with unsatisfactory patient outcomes despite advancements.
  • Rho-associated coiled-coil forming protein kinase 2 (ROCK2) is upregulated in RCC and linked to poorer survival, but its function is unclear.

Purpose of the Study:

  • To elucidate the molecular function and RNA interactions of ROCK2 in renal cell carcinoma.
  • To identify genes and alternative splicing events regulated by ROCK2 in RCC.

Main Methods:

  • RNA-sequencing (RNA-seq) analysis of ROCK2 knockdown versus control 786-O RCC cells.
  • Individual-nucleotide-resolution Cross-linking and Purification (iRIP-seq) to map ROCK2-RNA interactions.
  • Comparative analysis of RNA-seq and iRIP-seq data.

Main Results:

  • Identified 464 differentially expressed genes and 1287 alternative splicing events regulated by ROCK2.
  • iRIP-seq revealed ROCK2 RNA binding biases in 5' UTR, intronic, and intergenic regions.
  • 292 overlapping genes between ROCK2-regulated splicing and RNA binding were enriched in tumorigenic pathways.

Conclusions:

  • Defined a comprehensive ROCK2-RNA interaction map in a human RCC cell line.
  • Demonstrated ROCK2's role in regulating alternative splicing and gene expression in kidney cancer.
  • Provided insights into the molecular mechanisms of ROCK2 in RCC development and progression.

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