Oncotarget

Research Papers:

Transcriptome-wide analysis of compression-induced microRNA expression alteration in breast cancer for mining therapeutic targets

Baek Gil Kim _, Suki Kang, Hyun Ho Han, Joo Hyun Lee, Ji Eun Kim, Sung Hwan Lee and Nam Hoon Cho

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Oncotarget. 2016; 7:27468-27478. https://doi.org/10.18632/oncotarget.8322

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Abstract

Baek Gil Kim1,2, Suki Kang1,3, Hyun Ho Han2, Joo Hyun Lee2, Ji Eun Kim2, Sung Hwan Lee4, Nam Hoon Cho1,2,3,5

1Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea

2Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea

3Severance Biomedical Science Institute (SBSI), Yonsei University College of Medicine, Seoul, South Korea

4Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea

5Global 5-5-10 System Biology, Yonsei University, Seoul, South Korea

Correspondence to:

Nam Hoon Cho, e-mail: [email protected]

Keywords: compression, microRNA, transcriptome, breast cancer, incurable cancer therapy

Received: November 23, 2015    Accepted: March 14, 2016    Published: March 24, 2016

ABSTRACT

Tumor growth–generated mechanical compression may increase or decrease expression of microRNAs, leading to tumor progression. However, little is known about whether mechanical compression induces aberrant expression of microRNAs in cancer and stromal cells. To investigate the relationship between compression and microRNA expression, microRNA array analysis was performed with breast cancer cell lines and cancer-associated fibroblasts (CAFs) exposed to different compressive conditions. In our study, mechanical compression induced alteration of microRNA expression level in breast cancer cells and CAFs. The alteration was greater in the breast cancer cells than CAFs. Mechanical compression mainly induced upregulation of microRNAs rather than downregulation. In a parallel mRNA array analysis, more than 25% of downregulated target genes were functionally involved in tumor suppression (apoptosis, cell adhesion, and cell cycle arrest), whereas generally less than 15% were associated with tumor progression (epithelial-mesenchymal transition, migration, invasion, and angiogenesis). Of all cells examined, MDA-MB-231 cells showed the largest number of compression-upregulated microRNAs. miR-4769-5p and miR-4446-3p were upregulated by compression in both MDA-MB-231 cells and CAFs. Our results suggest that mechanical compression induces changes in microRNA expression level, which contribute to tumor progression. In addition, miR-4769-5p and miR-4446-3p may be potential therapeutic targets for incurable cancers, such as triple negative breast cancer, in that this would reduce or prevent downregulation of tumor-suppressing genes in both the tumor and its microenvironment simultaneously.


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