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Colorectal cancer

miR-100 and miR-125b induce cetuximab resistance in CRC

Nature Reviews Gastroenterology & Hepatology volume 14, page 691 (2017)Cite this article

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Cetuximab is a monoclonal antibody therapy against epidermal growth factor receptor (EGFR), commonly used in patients with wild-type KRAS CRC. However, the development of treatment resistance is frequent, and research since the FDA approval of cetuximab for CRC in 2009 has sought to identify the key pathways involved. The discovery that long non-coding RNAs (lncRNAs) can modulate the expression of key oncogenic or tumour suppressor proteins prompted Yuanyuan Lu and colleagues to investigate the role of these regulatory transcripts in cetuximab resistance.

In 3D-cultured cetuximab-resistant CRC cells (known as cetuximab-resistant cystic colonies, or CC-CRs) derived from the HCA-7 cell line, the researchers first ruled out known causes of cetuximab resistance, including copy number variations, gene fusions and gene mutations reported in prior studies. Relative to cetuximab-sensitive cells, the lncRNA MIR100HG was the most upregulated transcript in CC-CRs. This lncRNA gives rise to three intronic miRs: miR-100, miR-125b and let-7a2; strikingly, miR-100 and miR-125b were the most upregulated miRs in CC-CR cells. Supporting the generalizability of these results, an assessment of 30 other CRC cell lines revealed a close association between degree of cetuximab resistance and expression of MIR100HG and its product miRs.

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References

  1. Lu, Y. et al. lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling. Nat. Med. http://dx.doi.org/10.1038/nm.4424 (2017)

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  1. Hugh Thomas
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Thomas, H. miR-100 and miR-125b induce cetuximab resistance in CRC. Nat Rev Gastroenterol Hepatol 14, 691 (2017). https://doi.org/10.1038/nrgastro.2017.156

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