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RNA-binding motif protein 10 induces apoptosis and suppresses proliferation by activating p53

Ji Hoon Jung1,2,3, Hyemin Lee1,2, Bo Cao1,2

  • 1Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana, 70112, USA.

Oncogene
|October 9, 2019
PubMed

Insights

RNA-binding motif protein 10 (RBM10) suppresses tumors by activating p53, inhibiting cancer cell growth and promoting apoptosis. This protein blocks the MDM2-p53 feedback loop, enhancing p53 stability and improving patient survival in lung cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • RNA-binding motif protein 10 (RBM10) is frequently altered in lung cancer.
  • RBM10 loss enhances tumor growth, suggesting a tumor suppressor role, but mechanisms are unclear.
  • RBM10 regulates splicing and proliferation, impacting cancer progression.

Purpose of the Study:

  • To elucidate the molecular mechanisms of RBM10's tumor suppressive function.
  • To investigate RBM10's role in apoptosis and cancer cell proliferation via p53 activation.
  • To analyze the correlation between RBM10, p53 status, and patient survival.

Main Methods:

  • Analysis of cancer genomic databases.
  • Overexpression and knockdown studies of RBM10 in cancer cells.
  • Assessment of p53 stability, ubiquitination, and MDM2-p53 interaction.
  • Evaluation of mitochondrial respiration, cell migration, and proliferation.

Main Results:

  • RBM10 activates p53, inducing apoptosis and inhibiting cancer cell proliferation.
  • Patients with wild-type RBM10 and p53 show longer survival.
  • RBM10 overexpression inhibits proliferation, migration, and mitochondrial respiration in p53 wild-type cancer cells.
  • RBM10 stabilizes p53 by disrupting the MDM2-p53 interaction, reducing p53 ubiquitination.

Conclusions:

  • RBM10 acts as a tumor suppressor by activating p53.
  • RBM10 inhibits cancer progression by blocking the MDM2-p53 feedback loop, stabilizing p53.
  • RBM10's role in p53 activation presents a potential therapeutic target for cancer treatment.

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