Ying Hanyue, Zhao Ruping, Yu Qingqing, Zhang Ke, Deng Qinghua
The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Radiotherapy, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Drug Dev Res. 2022 Apr;83(2):512-524. doi: 10.1002/ddr.21882. Epub 2021 Sep 19.
Circular RNAs (circRNAs) play vital regulatory roles in the development of ovarian cancer (OC). However, the functions of circRNA Atlastin GTPase 2 (circATL2) in paclitaxel (PTX) resistance of OC are still unclear. As a result, circATL2 was upregulated in PTX-resistant OC tissues and cells. CircATL2 knockdown reduced IC of PTX, inhibited colony formation ability and promoted cell cycle arrest and apoptosis in PTX-resistant OC cells. Silencing of circATL2 restrained PTX resistance in vivo. Furthermore, miR-506-3p could be targeted by circATL2 and miR-506-3p inhibition reversed the impacts of circATL2 knockdown on PTX resistance and cell progression in PTX-resistant OC cells. NFIB was identified as the target of miR-506-3p. MiR-506-3p overexpression suppressed PTX resistance and malignant behaviors of PTX-resistant OC cells, with NFIB elevation rescued the impacts. To summarize, circATL2 promoted the resistance of OC to PTX by sponging miR-506-3p to upregulate NFIB expression, providing a new sight in chemoresistance of OC.
环状RNA（circRNAs）在卵巢癌（OC）的发展中发挥着至关重要的调节作用。然而，环状RNA Atlastin GTP酶2（circATL2）在OC对紫杉醇（PTX）耐药性中的功能仍不清楚。结果显示，circATL2在PTX耐药的OC组织和细胞中上调。circATL2敲低降低了PTX的半数抑制浓度（IC），抑制了集落形成能力，并促进了PTX耐药OC细胞的细胞周期阻滞和凋亡。circATL2沉默在体内抑制了PTX耐药性。此外，circATL2可靶向miR-506-3p，抑制miR-506-3p可逆转circATL2敲低对PTX耐药OC细胞中PTX耐药性和细胞进程的影响。NFIB被确定为miR-506-3p的靶标。miR-506-3p过表达抑制了PTX耐药OC细胞的PTX耐药性和恶性行为，NFIB的升高挽救了这些影响。综上所述，circATL2通过海绵吸附miR-506-3p上调NFIB表达，促进OC对PTX的耐药性，为OC的化疗耐药性提供了新的见解。
