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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

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In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor

Hui Hong1,2, Shun Yao3,4, Yuanyuan Zhang5

  • 1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Plos Genetics
|November 2, 2020
PubMed

Insights

Researchers identified a new tumor-suppressive microRNA (miRNA), miR-190b, crucial in lung cancer development. A novel CRISPR/Cas9 system was used to screen miRNAs in a mouse model, revealing miR-190b

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are implicated in various cancers, but their role in initiating lung cancer is unclear.
  • Lung cancer remains a leading cause of cancer-related deaths globally.

Purpose of the Study:

  • To investigate the function of microRNAs in de novo lung tumorigenesis.
  • To develop and utilize an in vivo screening platform for functional miRNA analysis in genetically engineered mouse models (GEMMs).

Main Methods:

  • Development of a CRISPR/Cas9-mediated dual guide RNA (dgRNA) system for miRNA knockout in GEMMs.
  • Bioinformatic analysis of human lung cancer miRNA databases to identify downregulated miRNAs.
  • In vivo knockout screening of 16 candidate miRNAs in the KrasG12D/Trp53L/L (KP) mouse model.

Main Results:

  • Identification of miR-30b, miR-146a, and the novel tumor suppressor miR-190b as downregulated in lung cancer progression.
  • Overexpression of miR-190b suppressed malignant progression in the KP mouse model and human lung cancer cell lines.
  • miR-190b was found to target the Hus1 gene; Hus1 knockout also suppressed lung tumorigenesis in the KP model.

Conclusions:

  • The study established an effective in vivo miRNA knockout platform for functional screening in GEMMs.
  • miR-190b is identified as a novel tumor suppressor significantly inhibiting lung cancer development.
  • Targeting miR-190b or its downstream effector Hus1 presents a potential therapeutic strategy for lung cancer.

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