A-to-I RNA Edited miR-3167 Restrains Malignant Behaviors of Lung Adenocarcinoma by Influencing SSR2-Meditated Hippo Signaling

Mol Carcinog. 2025 Sep;64(9):1552-1563. doi: 10.1002/mc.70011. Epub 2025 Jul 9.

Abstract

Recently, RNA editing, as a natural modification process of RNA molecules, has aroused extensive interest in the scientific community. This study elaborated the role and process of A-to-I RNA edited miR-3167 in lung adenocarcinoma (LUAD). RT-qPCR and Western blot analysis were employed for the detection of miRNA and gene expressions. The function of miRNA was investigated through Transwell, CCK-8 and flow cytometry assays. Dual-luciferase reporter assay was conducted to assess the link between gene and miRNA. The level of A-to-I RNA editing for miR-3167 was declined in LUAD tissues, which was linked to adverse clinical outcomes and prognosis in LUAD patients. In LUAD, ADAR2 enzyme is responsible for mediating the A-to-I RNA editing of miR-3167. Functionally, LUAD cell viability and metastasis were scarcely influenced by wt-miR-3167, while miR-3167 displayed antitumor activity in LUAD post A-to-I RNA editing. Mechanically, SSR2 is directly targeted by ed-miR-3167 in LUAD, but not wt-miR-3167. SSR2 served as a tumor promoter in LUAD progression by inactivating Hippo signaling and hindering immune infiltration. Ed-miR-3167 exerted tumor inhibitory effect in LUAD by weakening the carcinogenesis of SSR2. A-to-I RNA edited miR-3167 curbs malignant behaviors of LUAD by activating Hippo signaling through downregulating SSR2, indicating that edited miR-3167 has the potential as a therapeutic target for LUAD.

Keywords: A‐to‐I RNA editing; Hippo signaling; SSR2; lung adenocarcinoma; miR‐3167.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / pathology
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hippo Signaling Pathway
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Male
  • Mice
  • MicroRNAs* / genetics
  • Prognosis
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • RNA Editing*
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Signal Transduction

Substances

  • MicroRNAs
  • Protein Serine-Threonine Kinases
  • RNA-Binding Proteins