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Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Kenzui Taniue1, Akiko Kurimoto2, Hironobu Sugimasa1

  • 1Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan;

Proceedings of the National Academy of Sciences of the United States of America
|January 16, 2016
PubMed

Insights

A novel long noncoding RNA, UPAT, is crucial for colorectal cancer cell survival and tumor growth. UPAT stabilizes the UHRF1 protein, impacting cancer progression and offering potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers.
  • lncRNAs play roles in tumor development by regulating gene expression.
  • Mechanisms include chromatin remodeling and transcriptional/posttranscriptional control.

Purpose of the Study:

  • To investigate the role of a specific lncRNA, UPAT, in colorectal cancer.
  • To elucidate the molecular mechanisms by which UPAT influences cancer cell survival and tumorigenicity.

Main Methods:

  • Identification and characterization of the UPAT lncRNA.
  • Analysis of UPAT's interaction with the UHRF1 protein.
  • Assessment of UHRF1 ubiquitination and degradation pathways.
  • Evaluation of UHRF1-regulated genes (SCD1, SPRY4) in colon tumor cells.

Main Results:

  • UPAT is essential for colorectal cancer cell survival and tumorigenicity.
  • UPAT stabilizes UHRF1 by inhibiting its ubiquitination and degradation.
  • UHRF1 up-regulates Stearoyl-CoA desaturase 1 (SCD1) and Sprouty 4 (SPRY4), which are vital for colon tumor cell survival.
  • This study demonstrates a lncRNA's role in regulating protein ubiquitination and degradation.

Conclusions:

  • UPAT plays a critical role in colorectal cancer by regulating UHRF1 stability and downstream targets.
  • UPAT and UHRF1 represent potential therapeutic targets for colon cancer treatment.
Keywords:
UHRF1UPATlong noncoding RNAtumorigenicityubiquitination

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