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Systematic identification of clinically relevant miRNAs for potential miRNA-based therapy in lung adenocarcinoma

Shu-Hsuan Liu1, Kai-Wen Hsu2, Yo-Liang Lai3,4

  • 1Research Center for Cancer Biology, China Medical University, Taichung 40402, Taiwan.

Molecular Therapy. Nucleic Acids
|June 18, 2021
PubMed

Insights

This study identifies three tumor suppressor microRNAs (miRNAs) that show promise for treating lung adenocarcinoma (LUAD). Combining these miRNAs effectively inhibited tumor growth and metastasis in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Lung adenocarcinoma (LUAD) is a leading cause of cancer death with limited treatment options for advanced stages.
  • There is a critical need for novel therapeutic strategies to improve outcomes for LUAD patients.

Purpose of the Study:

  • To identify novel tumor suppressor microRNAs (miRNAs) for potential LUAD therapy.
  • To evaluate the therapeutic efficacy of identified miRNAs, individually and in combination, against LUAD progression.

Main Methods:

  • Integrative analysis of LUAD miRNA sequencing (miRNA-seq) and RNA-seq data from The Cancer Genome Atlas (TCGA).
  • Identification of candidate miRNAs based on differential expression, survival significance, and target correlations.
  • In vitro and in vivo evaluation of miRNA mimics for anti-cancer effects.

Main Results:

  • Three candidate tumor suppressor miRNAs (miR-195-5p, miR-101-3p, miR-338-5p) were identified.
  • Combined mimics of these three miRNAs demonstrated superior efficacy in inhibiting LUAD cell growth and progression compared to single mimics.
  • Combined miRNA mimics significantly reduced tumor volume and metastasis in lung tumor animal models.

Conclusions:

  • The identified combination of miR-195-5p, miR-101-3p, and miR-338-5p holds significant therapeutic potential for treating LUAD.
  • This miRNA combination offers a promising new avenue for improving treatment outcomes in LUAD patients with poor prognoses.
Keywords:
additive effectlung adenocarcinomamiRNAmiRNA mimicsnucleotide drugtherapy

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