Loss of miR-200c : A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers

Abstract EN

We focus on unique roles of miR-200c in breast, ovarian, and endometrial cancers.

Members of the miR-200 family target ZEB1, a transcription factor which represses E-cadherin and other genes involved in polarity.

We demonstrate that the double negative feedback loop between miR-200c and ZEB1 is functional in some, but not all cell lines.

Restoration of miR-200c to aggressive cancer cells causes a decrease in migration and invasion.

These effects are independent of E-cadherin status.

Additionally, we observe that restoration of miR-200c to ovarian cancer cells causes a decrease in adhesion to laminin.

We have previously reported that reintroduction of miR-200c to aggressive cells that lack miR-200c expression restores sensitivity to paclitaxel.

We now prove that this ability is a result of direct targeting of class III beta-tubulin (TUBB3).

Introduction of a TUBB3 expression construct lacking the miR-200c target site into cells transfected with miR-200c mimic results in no change in sensitivity to paclitaxel.

Lastly, we observe a decrease in proliferation in cells transfected with miR-200c mimic, and cells where ZEB1 is knocked down stably, demonstrating that the ability of miR-200c to enhance sensitivity to paclitaxel is not due to an increased proliferation rate.