Int. J. Mol. Sci. 2014, 15(1), 1392-1401; doi:10.3390/ijms15011392
Article

Extracellular Disposal of Tumor-Suppressor miRs-145 and -34a via Microvesicles and 5-FU Resistance of Human Colon Cancer Cells

* email, email, email, email, email and email
Received: 8 November 2013; in revised form: 7 January 2014 / Accepted: 8 January 2014 / Published: 20 January 2014
(This article belongs to the Section Molecular Pathology)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: The dysregulation of microRNA (miRNA) expression causes various kinds of diseases. Especially, alterations in miRNA expression levels are frequently observed in human tumor cells and are associated with cancer pathogenesis. Earlier we established Fluorouracil (5-FU)-resistant human colon cancer DLD-1 cells (DLD-1/5FU) from parental 5-FU- sensitive DLD-1 cells. In the present study, we examined the expression of miRNA in each cell line and in its extracellular microvesicles (MVs) before and after treatment with 5-FU. The nascent RNAs of anti-oncogenic miR-34a and -145 labeled with EU in both cells were proved to be transferred into MVs in both cell lines. The levels of miR-34a and -145 in the cells and in their MVs were not largely different in the two cell lines, and a substantial amount of both miRNAs was secreted by both cell lines even in the steady-state condition. The exposure of both cell lines to 5-FU significantly increased the intracellular levels of miR-145 and miR-34a in the 5-FU-sensitive DLD-1 cells, whereas the level of neither miR was elevated in the DLD-1/5FU cells. Interestingly, the amount of miR-145 detected in the small MVs shed into the medium of the parental cells was reduced after the treatment with 5-FU. On the other hand, the intracellular expression of miR-34a in the DLD-1/5FU cells was down-regulated compared with that in the parental DLD-1 cells even in the steady-state condition. As to the miR-34a secreted into MVs, the increase in the level in DLD-1/5FU cells was greater than that in the parental DLD-1 cells after the treatment with 5-FU. Thus, the intra- and extracellular miR-145 and -34a were closely associated with 5-FU resistance, and the resistance was in part due to the enhanced secretion of miR-145 and -34a via MVs, resulting in low intracellular levels of both miRNAs.
Keywords: miR-34a; miR-145; 5-FU; microvesicles; drug resistance
PDF Full-text Download PDF Full-Text [531 KB, uploaded 19 June 2014 05:24 CEST]

Export to BibTeX |
EndNote


MDPI and ACS Style

Akao, Y.; Khoo, F.; Kumazaki, M.; Shinohara, H.; Miki, K.; Yamada, N. Extracellular Disposal of Tumor-Suppressor miRs-145 and -34a via Microvesicles and 5-FU Resistance of Human Colon Cancer Cells. Int. J. Mol. Sci. 2014, 15, 1392-1401.

AMA Style

Akao Y, Khoo F, Kumazaki M, Shinohara H, Miki K, Yamada N. Extracellular Disposal of Tumor-Suppressor miRs-145 and -34a via Microvesicles and 5-FU Resistance of Human Colon Cancer Cells. International Journal of Molecular Sciences. 2014; 15(1):1392-1401.

Chicago/Turabian Style

Akao, Yukihiro; Khoo, Fiona; Kumazaki, Minami; Shinohara, Haruka; Miki, Kohei; Yamada, Nami. 2014. "Extracellular Disposal of Tumor-Suppressor miRs-145 and -34a via Microvesicles and 5-FU Resistance of Human Colon Cancer Cells." Int. J. Mol. Sci. 15, no. 1: 1392-1401.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert