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Role of human noncoding RNAs in the control of tumorigenesis

Ling Li1, Tingting Feng, Yingying Lian

  • 1Center for Functional Genomics and Bioinformatics, College of Life Science, Sichuan University, Chengdu, Sichuan 610064, China.

Proceedings of the National Academy of Sciences of the United States of America
|July 24, 2009
PubMed

Insights

Human noncoding RNAs bind to PSF protein, releasing it from proto-oncogenes and activating transcription. This mechanism drives cancer development, with high levels of these PSF-binding RNAs found in tumor cells.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • The protein PSF normally represses proto-oncogene transcription.
  • Mouse VL30-1 RNA releases PSF, activating transcription and influencing tumorigenesis.
  • The role of human RNAs in this mechanism was previously unclear.

Purpose of the Study:

  • To investigate if human noncoding RNAs can replace VL30-1 RNA in regulating PSF and proto-oncogene transcription.
  • To determine the role of PSF-binding human RNAs in human cell tumorigenesis and cancer etiology.

Main Methods:

  • Affinity chromatography was used to isolate human noncoding RNA fragments that bind to human PSF (hPSF).
  • The tumorigenic potential of these RNA fragments was assessed in human melanoma and mouse fibroblast cell lines.
  • Tumorigenicity was evaluated by colony formation in agar and tumor formation in mice.
  • Expression levels of hPSF-binding RNAs were analyzed in human tumor lines versus fibroblast cells.

Main Results:

  • Five human noncoding RNA fragments binding to hPSF were identified, each mapping to a different gene.
  • Expression of these RNA fragments individually promoted tumorigenicity in human melanoma cells.
  • Knockdown of endogenous RNAs using shRNA suppressed tumorigenicity.
  • Expression of these RNAs induced transformation to tumorigenic cells in mouse NIH/3T3 cells.
  • Human tumor lines showed elevated expression of several hPSF-binding RNAs compared to fibroblasts.

Conclusions:

  • Human hPSF-binding RNAs drive cell transformation and tumorigenesis by releasing hPSF from proto-oncogenes.
  • Dysregulated expression of these RNAs plays a significant role in the development of human cancers.
  • This mechanism highlights a novel pathway in cancer etiology involving noncoding RNA-protein interactions.

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