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Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data
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Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data

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APC-activated long noncoding RNA inhibits colorectal carcinoma pathogenesis through reduction of exosome production

Feng-Wei Wang1, Chen-Hui Cao1, Kai Han1

  • 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

The Journal of Clinical Investigation
|December 5, 2018
PubMed

Insights

Adenomatous polyposis coli (APC) regulates lncRNA-APC1, a novel therapeutic target for colorectal cancer (CRC). Lower lncRNA-APC1 levels correlate with advanced CRC and poor prognosis, suggesting its potential in cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The adenomatous polyposis coli (APC) gene is crucial in colorectal cancer (CRC) pathogenesis, presenting drug development challenges.
  • Long noncoding RNAs (lncRNAs) are emerging as key players in cancer pathology and potential therapeutic targets.

Purpose of the Study:

  • To identify and characterize a novel APC-regulated lncRNA (lncRNA-APC1) in colorectal cancer.
  • To investigate the functional role of lncRNA-APC1 in CRC progression and its potential as a therapeutic target.

Main Methods:

  • lncRNA microarray screening to identify APC-activated lncRNAs.
  • Expression analysis of lncRNA-APC1 in a large cohort of CRC tissues.
  • Functional assays including cell growth, metastasis, and angiogenesis inhibition studies.
  • Investigation of molecular mechanisms involving PPARα, Rab5b mRNA, exosome production, and Wnt signaling.

Main Results:

  • lncRNA-APC1 expression is decreased in CRC tissues and associated with lymph node metastasis, advanced stage, and poor prognosis.
  • APC enhances lncRNA-APC1 expression by suppressing PPARα enrichment on its promoter.
  • Overexpression of lncRNA-APC1 inhibits CRC cell growth, metastasis, and angiogenesis by reducing exosome production via Rab5b mRNA destabilization.
  • Exosomes from lncRNA-APC1-silenced cells promote angiogenesis and CRC cell proliferation/migration via MAPK and noncanonical Wnt signaling.

Conclusions:

  • lncRNA-APC1 is a critical APC-regulated lncRNA involved in colorectal cancer pathogenesis.
  • The APC-lncRNA-APC1 axis represents a promising therapeutic strategy for colorectal cancer treatment.
Keywords:
Cell migration/adhesionColorectal cancerGastroenterologyOncology

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