The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Doxorubicin and Topotecan Resistant Ovarian Cancer Cell Lines

Abstract

Epithelial ovarian cancer has the highest mortality among all gynecological malignancies. The main reasons for high mortality are late diagnosis and development of resistance to chemotherapy. Resistance to chemotherapeutic drugs can result from altered expression of drug-resistance genes regulated by miRNA. The main goal of our study was to detect differences in miRNA expression levels in two doxorubicin (DOX)- and two topotecan (TOP)-resistant variants of the A2780 drug-sensitive ovarian cancer cell line by miRNA microarray. The next aim was to recognize miRNAs as factors responsible for the regulation of drug-resistance genes. We observed altered expression of 28 miRNA that may be related to drug resistance. The upregulation of miR-125b-5p and miR-935 and downregulation of miR-218-5p was observed in both DOX-resistant cell lines. In both TOP-resistant cell lines, we noted the overexpression of miR-99a-5p, miR-100-5p, miR-125b-5p, and miR-125b-2-3p and decreased expression of miR-551b-3p, miR-551b-5p, and miR-383-5p. Analysis of the targets suggested that expression of important drug-resistant genes such as the collagen type I alpha 2 chain (COL1A2), protein Tyrosine Phosphatase Receptor Type K (PTPRK), receptor tyrosine kinase—EPHA7, Roundabout Guidance Receptor 2 (ROBO2), myristoylated alanine-rich C-kinase substrate (MARCK), and the ATP-binding cassette subfamily G member 2 (ABCG2) can be regulated by miRNA.

WITHDRAWN: Novel FOXM1 inhibitor STL001 sensitizes human cancers to a broad-spectrum of cancer therapies

“…The aberrant over-expression and activation of FOXM1 is the key molecular alteration in ovarian cancers and is associated with poor prognosis and chemotherapy resistance [2]. Doxorubicin is one of the most commonly used anticancer drugs approved by the FDA for ovarian cancer, and it is one of the most important drugs used as a second line of chemotherapy for platinum-resistant patients [49].…”

Identification of exosomal microRNAs and related hub genes associated with imatinib resistance in chronic myeloid leukemia

“…In the literature, increased expression of miR-99a-5p was reported in nonmuscle invasive bladder cancer (Kaba et al 2023), cisplatin-resistant esophageal cancer cells (Pandey et al 2023), topotecan resistant ovarian cancer cell lines (Stasiak et al 2022), cisplatin resistant ovarian cancer cell lines (Kazmierczak et al 2022), diffuse large B-cell lymphoma with chemotherapy resistance (Feng et al 2019), and signet-ring cell carcinoma, a histological subtype of gastric cancer (Saito et al 2020). In parallel with these studies, it has been shown that exosomal miR-99a-5p is elevated in the serum of ovarian cancer patients and promotes cancer cell invasion by increasing fibronectin and vitronectin expression in adjacent peritoneal mesothelial cells (Yoshimura et al 2018).…”

Drug resistance in ovarian cancer: from mechanism to clinical trial

“…miR-508-3p [ 29 ] and miR-134 [ 30 ], which are sponged by CircETDB1 and LINC01118, respectively, can posttranscriptionally regulate the expression of ABCC1. ABCG2 is involved in topotecan resistance in ovarian cancer, which is associated with miR-212-3p downregulation [ 31 ].…”