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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
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MicroRNA-410 acts as oncogene in NSCLC through downregulating SLC34A2 via activating Wnt/β-catenin pathway

Xuechao Zhang1, Xixian Ke1, Qiang Pu2

  • 1State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.

Oncotarget
|February 25, 2016
PubMed

Insights

MicroRNA-410 (miR-410) promotes non-small cell lung cancer (NSCLC) by downregulating SLC34A2. Restoring SLC34A2 reverses miR-410

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Solute carrier family 34 member 2 (SLC34A2) is downregulated in non-small cell lung cancer (NSCLC).
  • The precise mechanism behind SLC34A2's altered expression in NSCLC remains unclear.

Purpose of the Study:

  • To elucidate the regulatory relationship between miR-410 and SLC34A2 in NSCLC.
  • To investigate the role of the miR-410/SLC34A2 axis in NSCLC progression and the Wnt/β-catenin signaling pathway.

Main Methods:

  • Luciferase reporter assays to confirm direct targeting.
  • In vitro cell culture experiments assessing proliferation, invasion, and migration.
  • In vivo orthotopic xenograft mouse models.
  • Western blotting to analyze protein expression in the Wnt/β-catenin pathway.

Main Results:

  • miR-410 directly targets and inhibits SLC34A2 transcriptionally and post-transcriptionally.
  • miR-410 enhances NSCLC cell growth, invasion, and migration in vitro and in vivo.
  • Restoring SLC34A2 expression counteracts the pro-tumorigenic effects of miR-410.
  • An inverse correlation between miR-410 and SLC34A2 expression was observed in NSCLC tissues.
  • miR-410 activates the Wnt/β-catenin pathway by upregulating DVL2 and β-catenin, and downregulating Gsk3β, effects partially blocked by SLC34A2.

Conclusions:

  • miR-410 modulates SLC34A2 expression, contributing to NSCLC tumorigenesis and development.
  • The miR-410/SLC34A2 interaction promotes NSCLC via the Wnt/β-catenin signaling pathway.
  • miR-410 represents a potential therapeutic target for NSCLC.
Keywords:
NSCLCSLC34A2miR-410tumorigenesis and development

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