RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

Abstract

Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain-or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.

Circ_0030998 Promotes Tumor Proliferation and Angiogenesis by Sponging miR-567 to Regulate VEGFA in Colorectal Cancer

“…Taken together, these results suggested that Circ_0030998 promoted CRC cells proliferation and angiogenesis via miR-567. Previous studies showed that miR-567 could regulate KPNA4 21 , ATG5 22 and then inhibited tumor progression or chemoresistance. To explore the mechanism by which miR-567 inhibited CRC cells proliferation and angiogenesis, three miRNA databases were used to predict the potential target genes in the present study.…”

Extracellular Vesicle-Based Nucleic Acid Delivery: Current Advances and Future Perspectives in Cancer Therapeutic Strategies

“…For instance, miR-199a and miR-9 released via EVs enhanced chemosensitivity in a combinatorial protocol with temozolomide, leading to a significant reduction in proliferation, migration, and invasion of glioma [ 136 , 137 ]. In breast cancer, the use of exosomal miR-567 proved to be an effective means of reversing resistance to trastuzumab by inhibiting ATG5 expression [ 138 ] and miR-134 increased cisplatin-induced apoptosis by enhancing sensitivity to anti-Hsp90 drugs [ 13 ]. In liver cancer, miR-122 was found to be remarkably effective in decreasing chemoresistance by downregulating three genes, ADAM10, IGF1R, and CCNG1, involved in tumorigenesis and drug sensitivity.…”

Connecting the Missing Dots: ncRNAs as Critical Regulators of Therapeutic Susceptibility in Breast Cancer

“…In contrast, miR-16 acts as a tumor suppressor and can restore trastuzumab and lapatinib sensitivity by suppressing Cyclin J (CCNJ) and Far Upstream Element Binding Protein 1 (FUBP1) in resistant BC [105]. The exosomal transfer of miR-567 was recently reported to reverse trastuzumab resistance in BC via Autophagy related 5 (ATG5) inhibition; thereby, its therapeutic addition may considerably improve and enhance patients' responsiveness to this drug [106]. Other miRNAs with oncogenic or tumor suppressor functions in anti-HER2 drug resistance can be found in Table 2.…”