Abstract
Endometrial cancer (EC) is one of the most frequent gynecological tumors, and chemoresistance is a major obstacle to improving the prognosis of EC patients. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have recently emerged as crucial chemoresistance regulators that alter the levels of downstream target genes. Multidrug Resistance Protein 7 (MRP-7/ABCC10) is an ATP-binding cassette transporter that causes the resistance to anti-cancer drugs. The purpose of this research is to determine whether MRP-7 has a role in mediating the sensitivity of EC cells to paclitaxel and whether the expression of MRP-7 is regulated by miR-98 and lncRNA NEAT1. We reported that the levels of MRP-7 were significantly increased in EC tissues and associated with an unfavorable prognosis. Downregulation of MRP-7 in EC cells sensitized these cells to paclitaxel and reduced cell invasion. PLAUR serves as a downstream molecule of MRP-7 and facilitates paclitaxel resistance and EC cell invasiveness. Moreover, miR-98 serves as a tumor suppressor to inhibit MRP-7 expression, leading to the repression of paclitaxel resistance. Furthermore, a novel lncRNA, NEAT1, was identified as a suppressor of miR-98, and NEAT1 could upregulate MRP-7 levels by reducing the expression of miR-98. Taken together, these findings demonstrate that upregulation of MRP-7 and NEAT1, and downregulation of miR-98 have important roles in conferring paclitaxel resistance to EC cells. The modulation of these molecules may help overcome the chemoresistance against paclitaxel in EC cells.
Highlights
Endometrial cancer (EC) is the most prevalent type of gynecological cancer, with 382,000 new cases and approximately 90,000 deaths worldwide [1]
We investigated the role of MRP-7 in mediating EC cell paclitaxel sensitivity, as well as whether dysregulation of miR-98 and NEAT1 could regulate MRP-7 expression
Our findings showed that MRP-7 promotes paclitaxel resistance in EC cells, and its expression is regulated by the NEAT1/miR-98 pathway
Summary
Endometrial cancer (EC) is the most prevalent type of gynecological cancer, with 382,000 new cases and approximately 90,000 deaths worldwide [1]. The incidence of EC is rising [2]. The majority of EC are detected at an early stage and treated with surgery or a combination of treatments (including surgery, chemotherapy, radiation therapy, and potentially targeted therapy) [3]. Advanced and recurrent ECs, on the other hand, are difficult to cure. Resistance to treatment by EC cells is closely connected with poor survival of advanced and recurring ECs [4].
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