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

Authors
 Baek Gil Kim  ;  Suki Kang  ;  Hyun Ho Han  ;  Joo Hyun Lee  ;  Ji Eun Kim  ;  Sung Hwan Lee  ;  Nam Hoon Cho 
Citation
 Oncotarget, Vol.7(19) : 27468-27478, 2016 
Journal Title
 Oncotarget 
Issue Date
2016
MeSH
Breast Neoplasms/genetics* ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/genetics* ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Ductal, Breast/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; MCF-7 Cells ; MicroRNAs/biosynthesis* ; MicroRNAs/genetics ; Molecular Targeted Therapy ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Transcriptome ; Tumor Cells, Cultured ; Up-Regulation
Keywords
breast cancer ; compression ; incurable cancer therapy ; microRNA ; transcriptome
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.
Files in This Item:
T201603612.pdf Download
DOI
10.18632/oncotarget.8322
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
강숙희(Kang, Suki) ORCID logo https://orcid.org/0000-0002-9957-3479
김백길(Kim, Baek Gil) ORCID logo https://orcid.org/0000-0001-6270-1433
이성환(Lee, Sung Hwan)
조남훈(Cho, Nam Hoon) ORCID logo https://orcid.org/0000-0002-0045-6441
한현호(Han, Hyun Ho) ORCID logo https://orcid.org/0000-0002-6268-0860
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152039
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