microRNAs with AAGUGC seed motif constitute an integral part of an oncogenic signaling network

Y Zhou1, O Frings1, R M Branca1

  • 1Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.

Oncogene
|August 2, 2016
PubMed

Insights

Specific microRNAs (miRNAs) with an AAGUGC motif promote cancer cell growth and sensitivity to EGFR-targeted therapy. This discovery offers potential for improved cancer treatment selection.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • MicroRNA (miRNA) dysregulation is prevalent in cancer.
  • The precise functions of miRNAs in oncogenesis remain incompletely understood.
  • Identifying specific miRNAs driving cancer progression is crucial.

Purpose of the Study:

  • To identify oncogenic miRNAs in non-small cell lung cancer (NSCLC).
  • To assess the impact of identified miRNAs on response to epidermal growth factor receptor (EGFR)-targeting therapy.
  • To investigate the therapeutic potential of miRNA-based biomarkers.

Main Methods:

  • Functional genomics screens were employed to identify key miRNAs.
  • Global transcriptomics and proteomics analyses were performed.
  • Bioinformatic target prediction and clinical data analysis were utilized.

Main Results:

  • MiRNAs possessing an AAGUGC seed motif were found to enhance cancer cell proliferation.
  • These AAGUGC-motif miRNAs also increased sensitivity to EGFR inhibitors.
  • Identified targets included tumor suppressors regulating the G1/S cell cycle transition.

Conclusions:

  • The AAGUGC seed motif is proposed as an 'oncomotif' driving cancer proliferation.
  • Oncomotif-miRNAs contribute to cancer cell growth and may influence therapeutic response.
  • Findings suggest potential for patient stratification in EGFR-targeted therapies.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.6K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
4.2K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.5K
MicroRNAs01:22

MicroRNAs

12.0K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K