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MicroRNA-143/Musashi-2/KRAS cascade contributes positively to carcinogenesis in human bladder cancer

Takuya Tsujino1,2, Nobuhiko Sugito1, Kohei Taniguchi3

  • 1United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.

Cancer Science
|May 9, 2019
PubMed

Insights

MicroRNA-143 (miR-143) suppresses bladder cancer by inhibiting Musashi-2 (MSI2). This mechanism downregulates KRAS expression, offering a new therapeutic target for bladder cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-143 (miR-143) is downregulated in human bladder cancer (BC).
  • Mutations in FGFR3, RAS, and PIK3CA genes are common in BC and linked to RAS signaling.
  • miR-143 has been previously shown to inhibit RAS signaling and suppress cell growth in various cancers, including BC.

Purpose of the Study:

  • To investigate the regulatory role of miR-143 in bladder cancer.
  • To elucidate the molecular mechanism by which miR-143 affects RAS signaling in BC.
  • To identify novel therapeutic targets for bladder cancer based on miR-143 function.

Main Methods:

  • Utilized BC cell lines to study the effects of synthetic miR-143.
  • Investigated the interaction between miR-143 and Musashi-2 (MSI2) at the RNA level.
  • Analyzed the regulation of KRAS expression by MSI2 through direct mRNA binding and translation promotion.

Main Results:

  • Synthetic miR-143 was found to negatively regulate MSI2 expression in BC cell lines.
  • MSI2 was identified as a positive regulator of KRAS expression, binding directly to KRAS mRNA and enhancing its translation.
  • miR-143 effectively silenced both MSI2 and KRAS, leading to a downregulation of KRAS expression via the MSI2/KRAS pathway.

Conclusions:

  • miR-143 plays a crucial role in suppressing bladder cancer by targeting the MSI2/KRAS signaling cascade.
  • The findings reveal a novel mechanism of miR-143 action in BC, highlighting MSI2 as a key mediator.
  • Targeting the miR-143/MSI2/KRAS pathway presents a potential therapeutic strategy for bladder cancer treatment.
Keywords:
KRASMusashi-2RNA-binding proteinbladder cancermiR-143

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