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Tumour invasion and metastasis initiated by microRNA-10b in breast cancer

Author

Listed:
  • Li Ma

    (Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA)

  • Julie Teruya-Feldstein

    (Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA)

  • Robert A. Weinberg

    (Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA)

Abstract

MicroRNAs have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that some microRNAs can function as oncogenes or tumour suppressors, the role of microRNAs in mediating cancer metastasis remains unexplored. Here we show, using a combination of mouse and human cells, that microRNA-10b (miR-10b) is highly expressed in metastatic breast cancer cells and positively regulates cell migration and invasion. Overexpression of miR-10b in otherwise non-metastatic breast tumours initiates robust invasion and metastasis. Expression of miR-10b is induced by the transcription factor Twist, which binds directly to the putative promoter of mir-10b (MIRN10B). The miR-10b induced by Twist proceeds to inhibit translation of the messenger RNA encoding homeobox D10, resulting in increased expression of a well-characterized pro-metastatic gene, RHOC. Significantly, the level of miR-10b expression in primary breast carcinomas correlates with clinical progression. These findings suggest the workings of an undescribed regulatory pathway, in which a pleiotropic transcription factor induces expression of a specific microRNA, which suppresses its direct target and in turn activates another pro-metastatic gene, leading to tumour cell invasion and metastasis.

Suggested Citation

  • Li Ma & Julie Teruya-Feldstein & Robert A. Weinberg, 2007. "Tumour invasion and metastasis initiated by microRNA-10b in breast cancer," Nature, Nature, vol. 449(7163), pages 682-688, October.
  • Handle: RePEc:nat:nature:v:449:y:2007:i:7163:d:10.1038_nature06174
    DOI: 10.1038/nature06174
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    Cited by:

    1. Fabricio F Costa & Jared M Bischof & Elio F Vanin & Rishi R Lulla & Min Wang & Simone T Sredni & Veena Rajaram & Maria de Fátima Bonaldo & Deli Wang & Stewart Goldman & Tadanori Tomita & Marcelo B Soa, 2011. "Identification of MicroRNAs as Potential Prognostic Markers in Ependymoma," PLOS ONE, Public Library of Science, vol. 6(10), pages 1-10, October.
    2. Sheng, Tianhong & Li, Bing & Solea, Eftychia, 2023. "On skewed Gaussian graphical models," Journal of Multivariate Analysis, Elsevier, vol. 194(C).
    3. Krishnaveni M, 2017. "Epithelial Mesenchymal Transition as Targets for Cancer Therapy," Novel Approaches in Drug Designing & Development, Juniper Publishers Inc., vol. 3(1), pages 14-18, November.
    4. Emőke-Ágnes Horvát & Jitao David Zhang & Stefan Uhlmann & Özgür Sahin & Katharina Anna Zweig, 2013. "A Network-Based Method to Assess the Statistical Significance of Mild Co-Regulation Effects," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-14, September.
    5. Ying Wang & Xiushan Zheng & Zhiyong Zhang & Jinfeng Zhou & Guohong Zhao & Jianjun Yang & Limin Xia & Rui Wang & Xiqiang Cai & Hao Hu & Cailin Zhu & Yongzhan Nie & Kaichun Wu & Dexin Zhang & Daiming Fa, 2012. "MicroRNA-149 Inhibits Proliferation and Cell Cycle Progression through the Targeting of ZBTB2 in Human Gastric Cancer," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-10, October.
    6. Dahu Chen & Yutong Sun & Yuan Yuan & Zhenbo Han & Peijing Zhang & Jinsong Zhang & M James You & Julie Teruya-Feldstein & Min Wang & Sumeet Gupta & Mien-Chie Hung & Han Liang & Li Ma, 2014. "miR-100 Induces Epithelial-Mesenchymal Transition but Suppresses Tumorigenesis, Migration and Invasion," PLOS Genetics, Public Library of Science, vol. 10(2), pages 1-14, February.
    7. San-Nung Chen & Renin Chang & Li-Te Lin & Chyi-Uei Chern & Hsiao-Wen Tsai & Zhi-Hong Wen & Yi-Han Li & Chia-Jung Li & Kuan-Hao Tsui, 2019. "MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities," IJERPH, MDPI, vol. 16(9), pages 1-14, April.

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