Oncotarget

Research Papers:

MicroRNA 10b promotes abnormal expression of the proto-oncogene c-Jun in metastatic breast cancer cells

Revital Knirsh, Iris Ben-Dror, Shira Modai, Noam Shomron and Lily Vardimon _

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

Oncotarget. 2016; 7:59932-59944. https://doi.org/10.18632/oncotarget.11000

Metrics: PDF 658 views  |   HTML 1183 views  |   ?  


Abstract

Revital Knirsh1, Iris Ben-Dror1, Shira Modai2, Noam Shomron2, Lily Vardimon1

1Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

2Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Correspondence to:

Lily Vardimon, email: vardi@post.tau.ac.il

Keywords: miR10-b, c-Jun, NF1, RhoC, metastatic breast cancer

Received: March 15, 2016     Accepted: June 30, 2016     Published: August 2, 2016

ABSTRACT

MicroRNAs have been shown to act as oncogenes or tumor suppressers via various cellular pathways. Specifically, in breast cancer, upregulation of miR-10b is positively associated with aggressiveness of tumors. However, the mechanism by which miR-10b contributes to cell malignancy is largely unknown. Here we show that at the receiving end of the miR-10b pathway is the proto-oncogene c-Jun, a transcription factor that plays a critical role in stimulation of cell proliferation and tumor progression. c-Jun is known to be translationally activated by loss of cell contacts or restructuring of the cytoskeleton. A comprehensive analysis of miRNA expression exhibited a significant increase in miR-10b expression. This was supported by analysis of breast cancer cells, which showed that loss of E-cadherin in metastatic cells is accompanied by elevation of miR-10b and interestingly, by a marked increase in accumulation of c-Jun. Silencing miR-10b in metastatic breast cancer cells leads to a decline in c-Jun expression, whereas overexpression of miR-10b in HaCaT cells is sufficient to elevate the accumulation of c-Jun. The increase in c-Jun protein accumulation in metastatic cells is not accompanied by an increase in c-Jun mRNA and is not dependent on MAPK activity. Knockdown and overexpression experiments revealed that the increase is mediated by NF1 and RhoC, downstream targets of miR-10b that affect cytoskeletal dynamics through the ROCK pathway. Overall, we show the ability of miR-10b to activate the expression of c-Jun through RhoC and NF1, which represents a novel pathway for promoting migration and invasion of human cancer cells.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 11000