Circ-ABCB10 Contributes to Paclitaxel Resistance in Breast Cancer Through Let-7a-5p/DUSP7 Axis

Weiping Yang,1 Piguo Gong,1 Yifeng Yang,1 Chunyan Yang,2 Baohui Yang,3 Lijun Ren1 1Department of Thyroid Breast Surgery, Qingdao Chengyang People’s Hospital, Qingdao 266109, Shandong, People’s Republic of China; 2Obstetric Breast Health Clinic, Qingdao Haici Medical Center, Qingdao 266033, Shandong, People’s Republic of China; 3Department of Internal Medicine, Qingdao Chengyang Second People’s Hospital, Qingdao 266109, Shandong, People’s Republic of ChinaCorrespondence: Lijun RenDepartment of Thyroid Breast Surgery, Qingdao Chengyang People’s Hospital, No. 600, Changcheng Road, Chengyang District, Qingdao, Shandong, People’s Republic of ChinaEmail eijylo@163.comBackground: Paclitaxel (PTX) is one of the widely used chemotherapy drugs in breast cancer (BC) treatment. Unfortunately, the survival rate of metastatic BC patients remains poor due to PTX resistance. Therefore, uncovering the underlying mechanism behind the PTX resistance of BC cells is crucial for BC therapy.Methods: The enrichment of circular RNA ATP binding cassette subfamily B member 10 (circ-ABCB10), let-7a-5p and dual specificity phosphatase 7 (DUSP7) was measured by quantitative real time polymerase chain reaction (qRT-PCR) in PTX-resistant and PTX-sensitive BC tissues and cells. Chemoresistance, apoptosis, invasion and autophagy of BC cells were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell invasion assay and Western blot assay, respectively. The binding sites between let-7a-5p and circ-ABCB10 or DUSP7 were predicted by Starbase bioinformatic software, and the combination was confirmed by dual-luciferase reporter assay. The protein expression of DUSP7 was examined by Western blot assay. Murine xenograft model was established to confirm the role of circ-ABCB10 in vivo.Results: Circ-ABCB10 depletion promoted the PTX sensitivity and apoptosis while suppressed the invasion and autophagy of PTX-resistant BC cells. Circ-ABCB10 could bind to let-7a-5p in BC cells, and circ-ABCB10 contributed to PTX resistance of BC cells via let-7a-5p. DUSP7 is a direct target of let-7a-5p in BC cells, and the accumulation of DUSP7 reversed the promoting effects of let-7a-5p overexpression on the PTX sensitivity and apoptosis and the inhibitory impact on the invasion and autophagy of PTX-resistant BC cells. Circ-ABCB10 interference suppressed the growth of BC tumors in vivo.Conclusion: Circ-ABCB10 mediated PTX resistance, apoptosis, invasion and autophagy of BC cells via let-7a-5p/DUSP7 axis.Keywords: breast cancer, paclitaxel, chemoresistance, circ-ABCB10, let-7a-5p, DUSP7