RETRACTED: Exosomal MicroRNA-221-3p Confers Adriamycin Resistance in Breast Cancer Cells by Targeting PIK3R1

Abstract

Drug resistance in breast cancer (BC) cells continues to be a stern obstacle hindering BC treatment. Adriamycin (ADR) is a frequently employed chemotherapy agent used to treat BC. The exosomal transfer of microRNAs (miRNAs) has been reported to enhance the drug-resistance of BC cells. Herein, we first sought to elucidate the possible role of the exosomal transfer of miR-221-3p in the drug resistance of MCF-7 cells to ADR. Differentially expressed genes (DEGs) were initially screened through microarray analysis in BC drug resistance-related datasets. Next, the expression of miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was quantified in ADR-resistant MCF-7 (MCF-7/ADR) and ADR-sensitive MCF-7 (MCF-7/S) cell lines, after which exosomes were separated and identified in each cell line. Target relationship between miR-221-3p and PIK3R1 was validated by a dual-luciferase reporter assay. Next, the expression of miR-221-3p and PIK3R1 was altered to clarify their effects on the resistance of MCF-7 cells to ADR in vitro and in vivo. PIK3R1 was identified as a BC drug resistance-related DEG, with the regulatory miR-221-3p subsequently obtained. Moreover, the MCF-7/ADR cells exhibited a low expression of PIK3R1 and a high expression of miR-221-3p. Notably, PIK3R1 was identified as a target gene of miR-221-3p. The overexpression of miR-221-3p in MCF-7/ADR cell-derived exosomes promoted ADR resistance in MCF-7/S cells via the PI3K/AKT signaling pathway. The in vitro results were reproducible in in vivo assays. Taken together, drug-resistant BC cell-derived exosomal miR-221-3p can promote the resistance of BC cells to ADR by targeting PIK3R1 via the PI3K/AKT signaling pathway in vitro and in vivo. These findings provide encouraging insights and provide perspectives for further investigation into the BC drug resistance mechanism.

Exosome-Derived LncRNAs in Lung Cancer

“…For example, plasma exosomal proteins derived from endothelial cells play an important role in small cerebral vascular disease caused by Alzheimer's disease (53). Exosomes shuttling high levels of microRNA-221-3p promote the resistance of breast cancer cells to adriamycin by targeting PIK3R1 (54).…”

Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness

“…miR-221 is overexpressed in a variety of epithelial cancers including breast, liver, bladder, pancreas, gastric, colorectal cancer, melanoma, papillary thyroid carcinoma and glioblastoma [ 33 ]. Additionally, miR-221 has been found to be related to cancer progression in cervical squamous cell carcinoma [ 43 ], confers adriamycin resistance in breast cancer [ 44 ], and is a biomarker in hepatocellular carcinoma [ 45 ], diffuse large B cell lymphomas [ 46 ] and lung adenocarcinoma [ 47 ].…”

Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer

“…For instance, miR-221-3p is transcriptionally activated by Twist family BHLH transcription factor 2 ( TWIST2 ) and enhances cell migration, invasion, and lymphatic metastasis in cervical cancer [ 64 ]. Additionally, miR-221-3p mediates doxorubicin resistance in breast cancer cells [ 65 ]. In PaC, miR-221-3p can promote EMT by targeting RB transcriptional corepressor 1 ( RB1 ), thereby desensitizing cells to 5-FU [ 47 ] ( Figure 1 and Table 1 ).…”