TITLE:
Non-vesicle-bound free microRNAs could enter cells and affect gene expression
AUTHORS:
Gang Wang, Ka-Bik Lai, Bonnie Ching-Ha Kwa, Kai-Ming Chow, Philip Kam-Tao Li, Cheuk-Chun Szeto
KEYWORDS:
Cell Signaling; Fibrosis; Cytokine
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.3 No.3,
June
19,
2012
ABSTRACT: Background: Cell-free microRNAs (miRNAs) exist in body fluid. Previous studies showed that cell-free mi-RNAs are partly bound in microvesicles, and could transfer between cells via fusion with cell membrane. Methods: We quantified the amount of a panel of mi-RNA targets in and outside microvesicles in human proximal tubular epithelial cell (HK2) medium by microarray and real-time quantitative polymerase chain reaction (RT-QPCR). Intercellular miRNA transfer was explored by medium transfer experiments. Results: We identified a portion of cell-free miRNAs that exists as non-vesicle bound, truly naked form. More importantly, these non-vesicle bound free miRNA could transfer between cells and exert biological effects. By miRNA microarray, we showed that the expression of many miRNA targets in HK-2 cells were altered, either up- or down-regulated, after exposure to extrinsic free miRNAs. The miRNA-200 family was the most affected in our model, with a corresponding alteration in the messenger RNA expression of down-stream targets including ZEB1 and vimentin. Conclusion: Our results suggest that free miRNA may serve as an intercellular messenger, a phenomenon that needs further exploration.