A Novel miR-98 Negatively Regulates the Resistance of Endometrial Cancer Cells to Paclitaxel by Suppressing ABCC10/MRP-7

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.

Infigratinib (BGJ 398), a Pan-FGFR Inhibitor, Targets P-Glycoprotein and Increases Chemotherapeutic-Induced Mortality of Multidrug-Resistant Tumor Cells

“…These effects of PD 173074 were further reproduced by using the MRP7-overexpressing HEK293 cells, thereby illustrating its ability to interfere with ABCC10 [41]. Of note, multiple reports illustrate that besides P-glycoprotein, expression of ABCC10/MRP7 (unlike other MRPs) also contributes to the resistance of various cancer cells to taxanes [76,77] and can be utilized as a predictive biomarker for the resistance to PTX in several human malignancies, including a non-small cell lung cancer (NSCLC) [78], breast cancer [79] Strikingly, it was also shown that MRP7 can affect the in vivo tissue sensitivity to taxanes independently from ABCB1 [80].…”

Bioinformatics Analysis of Immune Cell Infiltration and Diagnostic Biomarkers between Ankylosing Spondylitis and Inflammatory Bowel Disease

“…Besides, one animal study showed that PLAUR played negative feedback regulation of glucocorticoid pathways in rats' ocular tissues [ 62 ]. Some scholars have found that PLAUR facilitated paclitaxel resistance and endometrial cancer cell invasiveness [ 63 ]. When epithelial cells moved and grew back when PLAUR was present, it made IBD less likely to happen [ 64 ].…”

Oncogenic circular RNA circ_0007534 contributes to paclitaxel resistance in endometrial cancer by sponging miR-625 and promoting ZEB2 expression

“…The failure of endometrial cancer treatment is closely associated with resistance to chemotherapy (such as Paclitaxel) ( 23 ). The mechanisms of Paclitaxel resistance are complex, including the aberrant expression of miRNAs and circRNAs ( 17 , 24 ). However, the roles of miRNAs and circRNAs in endometrial cancer chemoresistance are largely unknown.…”