A team of scientists led by Prof. LIU Mofang at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, have found that miR-155 suppresses ErbB2-induced malignant transformation.Thiswork entitled “miR-155 down-regulates ErbB2 and suppresses ErbB2-induced malignant transformation of breast epithelial cells” was published in Oncogene on April 11, 2016. The work was collaborated with Drs. Zhu Wei, Zhang Hongwei, and Dangsheng Li.
ErbB2 is overexpressed in ~25% of invasive/metastatic breast cancers and 50–60% of noninvasive ductal carcinomas in situ; thus, it has been documented as a vital oncogene in breast cancer. Stunning progress has been made in the development of targeted therapies for ErbB2-overexpressing cancers. In particular, Trastuzumab (Herceptin; Genentech, South San Francisco, CA, USA), a humanized anti-ErbB2 monoclonal antibody, has been used worldwide as an effective antitumor drug for ErbB2-positive breast cancer treatment. The administration of the drug to patients with ErbB2-positive breast tumors in combination or sequentially after chemotherapy resulted in a significant improvement in disease-free survival. Despite the well-defined outcome of ErbB2 overexpression in breast cancer, how ErbB2 is dysregulated in breast tumors remains incompletely understood.
He Xiaohong and his colleagues, under the supervision of Dr. LIU Mofang, found that ErbB2 expression is inversely correlated with the level of miR-155, a well-documented oncogenic miRNA, in ErbB2-positive breast tumors. We further determined that miR-155 potently suppresses ErbB2 in breast cancer cells. Mechanistically, miR-155 acts to down-regulate ErbB2 via two distinct mechanisms. First, miR-155 represses ErbB2 transcription by targeting HDAC2, a transcriptional activator of ErbB2. Second, miR-155 directly targets ErbB2 via a regulatory element in its coding region. Intriguingly, miR-155 is up-regulated by Trastuzumab and in turn leads to a reduction of ErbB2 expression in Trastuzumab-treated ErbB2-positive breast cancer cells. Functional studies showed that miR-155 inhibits ErbB2-induced malignant transformation of human breast epithelial cells. Thus, our findings reveal an intriguing miR-155-ErbB2 context in regulating the malignant transformation of breast epithelial cells, and thereby indicate a novel mode of action for miR-155 in ErbB2-positive breast cancer.
This study was supported by the grants from the Chinese Academy of Sciences, the Ministry of Science and Technology, National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.
KEYWORDS: miR-155; ErbB2; Trastuzumab; breast cancer
AUTHOR CONTACT:
LIU Mofang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai, China
Phone: 86-21-54921146;
E-mail: mfliu@sibcb.ac.cn
Article Link: http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016132a.html
A model of miR-155 as a key regulator in ErbB2-induced transformation of breast epithelial cells and Trastuzumab therapy response of ErbB2-positive breast cancer. (Image provided by Dr. LIU Mofang)
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