Abstract 88: The role of RBPMS in cisplatin resistant ovarian cancer

Abstract

Epithelial ovarian cancer is the fifth leading cause of cancer-associated deaths among women in the United States. High-grade serous ovarian cancer (HGSOC) is the most common type of epithelial ovarian cancer and accounts for 70-80% of ovarian cancer patient deaths. RNA-Binding Protein With Multiple Splicing (RBPMS) is a member of a family of proteins that bind to the nascent RNA transcripts and regulate their processing, including the pre-mRNA splicing and the transport, localization, and stability of the RNA molecules. However, little is known about the biological function of RBPMS family in ovarian cancer. We hypothesized that decreasing the expression of RBPMS in high-grade serous ovarian cancer increases ovarian cancer progression and platinum-based drug resistance. Quantitative real-time PCR (qPCR) and Western blot (WB) analysis were conducted to determine the basal mRNA and protein expression of RBPMS in ovarian cancer cells. The invasion ability of the ovarian cancer cells after targeting RBPMS with silencing RNA (siRNA) was determined by invasion assays. The proliferation rate of the ovarian cancer cells overexpressing RBPMS was determine by colony formation assay. RBPMS is highly expressed in A2780 cells when compared to the cisplatin resistance ovarian cancer cells and HGSOC cancer cells. Targeting RBPMS increased the invasion ability of the A2780 cells. Cisplatin resistant, A2780CP20 cells overexpressing RBPMS showed a decreased in cell proliferation when compared to the A2780CP20 empty vector clones. We described here for the first time the mRNA and protein expression profile of RBPMS in HGSOC and epithelial ovarian cancer cells. These studies will help to better understand the role of RBPMS in ovarian cancer and may support the use of RBPMS as an adjuvant treatment to overcome the platinum-based chemotherapy resistance characteristic of the high-grade serous ovarian cancer. Note: This abstract was not presented at the meeting. Citation Format: Perla M. Báez-Vega, Fatma Valiyeva, Ginette Santiago, Pablo Vivas-Mejia. The role of RBPMS in cisplatin resistant ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 88. doi:10.1158/1538-7445.AM2017-88

RBPMS is differentially expressed in high-grade serous ovarian cancers.

“…Multiple studies implicate RBPMS in some aspect of ovarian cancer pathogenesis and in the biology of other human cancers. RBPMS is over-expressed in the A2780 cervical cancer cell line and depletion of RBPMS in A2780 cells using small interfering RNA (siRNA) resulted in an increase in invasive potential, while over-expression of RBPMS in cisplatin-resistant A2780CP20 cells resulted in decreases in cell proliferation 15 . A study identifying differentially expressed genes between recurrent and non-recurrent ovarian cancer found that RBPMS was among the most differentially expressed genes (DEGs) between these groups and formed a node when generating a protein-protein interaction network based on interaction between DEGs (16).…”

Effect of valproic acid on cisplatin-resistant ovarian cancer cell lines

“…Cisplatin is one of the most important anticancer compounds used in the first line of chemotherapy for the treatment of ovarian cancer (15). Resistance to chemotherapeuic drugs including cisplatin, is a hindrance to successful chemotherapy in the patients with ovarian cancer (16,17). Therefor, new modalities are needed to overcome drug resistance (17,18).…”

“…Resistance to chemotherapeuic drugs including cisplatin, is a hindrance to successful chemotherapy in the patients with ovarian cancer (16,17). Therefor, new modalities are needed to overcome drug resistance (17,18). VPA is a short chain fatty acid which is used in the treatment of various neurological disorders including seizures, bipolar disorder, and migraine (19).…”