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

• Yusheng Wu ^[2] ; Wenwei Zhao ^[1] ; Yang Liu ^[1] ; Xiangtian Tan ^[1] ; Xin Li ^[1] ; Qin Zou ^[1] ; Zhengtao Xiao ^[2] ; Hui Xu ^{[2] [1]} ; Yuting Wang ^[1] ; Xuerui Yang ^[2]
  1. [1] Tsinghua University

     Tsinghua University

     China

     
  2. [2] 1 Tsinghua‐Peking Joint Center for Life Sciences Beijing China; 2 MOE Key Laboratory of Bioinformatics Tsinghua University Beijing China; 3 Center for Synthetic & Systems Biology Tsinghua University Beijing China; 4 School of Life Sciences Tsinghua University Beijing China
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 37, Nº. 23, 2018
• Idioma: inglés
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• Resumen

  • Elevated expression of RNA binding protein HNRNPC has been reported in cancer cells, while the essentialness and functions of HNRNPC in tumors were not clear. We showed that repression of HNRNPC in the breast cancer cells MCF7 and T47D inhibited cell proliferation and tumor growth. Our computational inference of the key pathways and extensive experimental investigations revealed that the cascade of interferon responses mediated by RIG‐I was responsible for such tumor‐inhibitory effect. Interestingly, repression of HNRNPC resulted in accumulation of endogenous double‐stranded RNA (dsRNA), the binding ligand of RIG‐I. These up‐regulated dsRNA species were highly enriched by Alu sequences and mostly originated from pre‐mRNA introns that harbor the known HNRNPC binding sites. Such source of dsRNA is different than the recently well‐characterized endogenous retroviruses that encode dsRNA. In summary, essentialness of HNRNPC in the breast cancer cells was attributed to its function in controlling the endogenous dsRNA and the down‐stream interferon response. This is a novel extension from the previous understandings about HNRNPC in binding with introns and regulating RNA splicing.