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Negative feedback regulation of AXL by miR-34a modulates apoptosis in lung cancer cells

Chun-Yu Cho1, Jhy-Shrian Huang2, Shine-Gwo Shiah3

  • 1National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan Department of Life Sciences, National Central University, Taoyuan 32001, Taiwan.

RNA (New York, N.Y.)
|December 16, 2015
PubMed

Insights

A novel feedback loop between AXL and microRNA-34a (miR-34a) was discovered, regulating cancer progression. This AXL-miR-34a interaction offers a new target for anticancer therapies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • AXL receptor tyrosine kinase is overexpressed in various cancers, driving invasion, metastasis, and chemoresistance.
  • Understanding the regulatory mechanisms of AXL is crucial for developing effective cancer treatments.

Purpose of the Study:

  • To elucidate the post-transcriptional regulatory feedback loop involving AXL and microRNAs (miRNAs).
  • To identify specific miRNAs and signaling pathways involved in AXL autoregulation.

Main Methods:

  • Bioinformatic analysis and molecular techniques were employed.
  • Investigated the role of AXL domains, phosphorylation sites, and miRNA targeting.
  • Examined the involvement of the JNK signaling pathway and ELK1 transcription factor.

Main Results:

  • A regulatory feedback loop between AXL and miR-34a was identified.
  • miR-34a targets AXL mRNA's 3' UTR, inhibiting AXL expression.
  • AXL overexpression induces miR-34a via ELK1 activation through the JNK pathway.
  • ELK1 overexpression promotes apoptosis by down-regulating AXL.

Conclusions:

  • AXL is autoregulated by miR-34a in a feedback loop.
  • This AXL-miR-34a axis presents a potential therapeutic target for novel anticancer strategies.
Keywords:
AXLELK1JNKapoptosisfeedback loop regulationmiR-34a

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