Overexpression of miR-200s inhibits proliferation and invasion while increasing apoptosis in murine ovarian cancer cells.

ABSTRACT

Women diagnosed with ovarian cancer frequently have a poor prognosis as their cancer is often diagnosed at more advanced stages when the cancer has metastasized. At this point surgery cannot remove all the tumor cells and while ovarian cancer cells often initially respond to chemotherapeutic agents like carboplatin and paclitaxel, resistance to these agents frequently occurs. Thus, novel therapies are required for the treatment of advanced stage ovarian cancer. One therapeutic option being explored is the regulation of non-coding RNAs such as microRNAs. An advantage of microRNAs is that they can regulate tens, hundreds and sometimes thousands of mRNAs in cells and thus may be more effective than chemotherapeutic agents or targeted therapies. To investigate the therapeutic potential of miR-200s in ovarian cancer, lentiviral vectors were used to overexpress both miR-200 clusters in two murine ovarian cancer cell lines, ID8 and 28-2. Overexpression of miR-200s reduced the expression of several mesenchymal genes and proteins, significantly inhibited proliferation as assessed by BrdU flow cytometry and significantly reduced invasion through Matrigel coated transwell inserts in both cell lines. Overexpression of miR-200s also increased basal apoptosis approximately 3-fold in both cell lines as determined by annexin V flow cytometry. Pathway analysis of RNA sequencing of control and miR-200 overexpressing ovarian cancer cells revealed that genes regulated by miR-200s were involved in processes like epithelial mesenchymal transition (EMT) and cell migration. Therefore, miR-200s can inhibit proliferation and increase apoptosis while suppressing tumor cell invasion and thus simultaneously target three key cancer pathways.