CircCYP24A1 hampered malignant phenotype of renal cancer carcinoma through modulating CMTM-4 expression via sponging miR-421

Cell Death Dis. 2022 Feb 26;13(2):190. doi: 10.1038/s41419-022-04623-0.

Abstract

Renal cell carcinoma (RCC) is a lethal urinary malignancy. Circular RNAs (circRNAs) contribute to the malignant phenotype and progression of several types of human cancers, including RCC. In this study, we identified relatively low hsa_circ_0060927 (circCYP24A1) expression in RCC tissue through high-throughput sequencing and RT-qPCR. Fluorescence in situ hybridization (FISH) was used to validate the expression and subcellular localization of circCYP24A1 in RCC tissues. CCK-8, Transwell, EdU, and wound-healing assays indicated that circCYP24A1 overexpression inhibited the proliferation, invasion, and migration of RCC cells. Dual-luciferase reporter, RNA immunoprecipitation (RIP), FISH, and RNA-pulldown assays verified that circCYP24A1 inhibited RCC progression by sponging miR-421, thus inducing CMTM-4 expression. Xenograft assays and metastasis models further indicated that circCYP24A1 significantly inhibited the metastasis and proliferation of RCC cells in vivo. Taken together, circCYP24A1 is a prognosis-related circRNA in RCC that functions through the circCYP24A1/miR-421/CMTM-4 axis to modulate RCC progression.

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kidney Neoplasms* / genetics
  • MARVEL Domain-Containing Proteins* / genetics
  • MicroRNAs* / genetics
  • Phenotype
  • RNA, Circular* / genetics
  • Vitamin D3 24-Hydroxylase

Substances

  • CMTM4 protein, human
  • MARVEL Domain-Containing Proteins
  • MIRN421 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase