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Function of HNRNPC in breast cancer cells by controlling the dsRNA-induced interferon response

Yusheng Wu1,2,3,4, Wenwei Zhao2,3,4, Yang Liu2,3,4,5

  • 1Tsinghua-Peking Joint Center for Life Sciences, Beijing, China.

The EMBO Journal
|August 31, 2018
PubMed

Insights

Repressing the RNA-binding protein HNRNPC inhibits breast cancer growth by triggering an interferon response. This occurs due to accumulated double-stranded RNA (dsRNA) from introns, a novel finding for HNRNPC function.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • Elevated expression of the RNA-binding protein HNRNPC is observed in cancer cells.
  • The precise role and essentiality of HNRNPC in tumor progression remain unclear.

Purpose of the Study:

  • To investigate the function and essentiality of HNRNPC in breast cancer cells.
  • To elucidate the molecular mechanisms underlying HNRNPC's role in tumor growth.

Main Methods:

  • Computational inference of key pathways.
  • Experimental investigations in MCF7 and T47D breast cancer cell lines.
  • Analysis of endogenous double-stranded RNA (dsRNA) accumulation and origin.

Main Results:

  • Repression of HNRNPC inhibited proliferation and tumor growth in breast cancer cells.
  • HNRNPC repression led to the accumulation of endogenous dsRNA, activating the RIG-I-mediated interferon response.
  • Accumulated dsRNA originated from pre-mRNA introns containing HNRNPC binding sites, distinct from retroviral sources.

Conclusions:

  • HNRNPC is essential for breast cancer cells, primarily through its regulation of endogenous dsRNA and downstream interferon responses.
  • This study reveals a novel function of HNRNPC in controlling dsRNA and innate immunity in cancer.
  • Findings extend previous knowledge of HNRNPC's role in RNA splicing and intron binding.
Keywords:
HNRNPCMCF7T47Dbreast cancerdouble‐stranded RNAinterferon responseinterferon signalingtumorigenesis

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