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MicroRNAs as Key Effectors in the p53 Network

Frauke Goeman1, Sabrina Strano1, Giovanni Blandino1

  • 1Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Rome, Italy.

International Review of Cell and Molecular Biology
|July 22, 2017
PubMed

Insights

The p53 protein network with MicroRNAs is crucial in cancer. Wild-type p53 suppresses tumors using MicroRNAs, while mutant p53 promotes cancer by hijacking this MicroRNA pathway.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • The p53 protein is a key regulator in cellular processes, including tumor suppression.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally.
  • The intricate relationship between p53 and miRNAs is vital for understanding cancer development.

Purpose of the Study:

  • To elucidate the complex interplay between p53 and MicroRNAs in cancer.
  • To investigate how wild-type and mutant p53 proteins differentially regulate and are regulated by MicroRNAs.
  • To explore the non-transcriptional roles of p53 in MicroRNA biogenesis and function.

Main Methods:

  • Analysis of transcriptional regulation of MicroRNAs by p53.
  • Investigation of MicroRNA-mediated regulation of p53.
  • Assessment of p53's role in MicroRNA biogenesis through interaction with the Microprocessor complex.
  • Examination of p53's modulation of MicroRNA-mRNA interactions via RISC complex and RNA-binding proteins.
  • Study of mutant p53's impact on MicroRNA processing and biogenesis factors like Dicer and KSRP.

Main Results:

  • Wild-type p53 directly regulates MicroRNA transcription for tumor suppression.
  • MicroRNAs control p53 expression by targeting it or related factors.
  • p53 modulates MicroRNA maturation and mRNA accessibility, influencing the MicroRNA-mRNA network.
  • Gain-of-function mutant p53 proteins utilize MicroRNAs to promote oncogenesis, including chemoresistance and metastasis.
  • Mutant p53 interferes with MicroRNA processing and downregulates key biogenesis factors.

Conclusions:

  • MicroRNAs are integral components of the p53 pathway, significantly impacting tumor development.
  • The context of wild-type versus mutant p53 dictates whether MicroRNAs combat or promote cancer.
  • Understanding the p53-MicroRNA axis is critical for developing novel cancer therapies.
Keywords:
AGOGain of functionMetastasisMicroRNAMicroRNA biogenesisMicroRNA maturationMicroprocessor complexMutant p53Transcriptional regulationTumor suppressorp53

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