Gao Yisheng, Liu Jie, Huan Jing, Che Fengyuan
Guangzhou University of Chinese Medicine, Guangzhou, 510006 Guangdong China.
Department of Urology, Linyi People's Hospital, Linyi, 276003 Shandong China.
Cancer Cell Int. 2020 Jul 22;20:334. doi: 10.1186/s12935-020-01421-6. eCollection 2020.
One of the main reasons for the failure of prostate cancer (PCa) treatment is the generation of chemoresistance. Circular RNA hsa_circ_0000735 (hsa_circ_0000735) is connected with the progression of cancer. Nevertheless, the role and regulatory mechanism of hsa_circ_0000735 in the resistance of PCa to docetaxel (DTX) are unclear.
Expression levels of hsa_circ_0000735 and miR-7-5p (miR-7) in tissue samples and cells were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The DTX sensitivity, viability, colony formation, cell cycle progression, and apoptosis of DTX-resistant PCa cells were determined via Cell Counting Kit-8 (CCK-8), cell colony formation, or flow cytometry assays. The levels of multidrug resistance protein 1 (MDR1) protein, cyclinD1, and B cell lymphoma 2 (bcl-2) were detected by western blotting. The interaction between hsa_circ_0000735 and miR-7 was verified via dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The role of hsa_circ_0000735 in vivo was validated through tumor formation experiments.
Hsa_circ_0000735 was upregulated and miR-7 was downregulated in DTX-resistant PCa tissues and cells. High hsa_circ_0000735 expression had a shorter overall survival. Both hsa_circ_0000735 knockdown and miR-7 mimic boosted DTX sensitivity, constrained viability, colony formation, cell cycle progression, and fostered apoptosis of DTX-resistant PCa cells. Also, hsa_circ_0000735 silencing elevated DTX sensitivity and repressed tumor growth in PCa in vivo. Mechanistically, hsa_circ_0000735 served as a sponge for miR-7. MiR-7 inhibition overturned hsa_circ_0000735 silencing-mediated impacts on DTX sensitivity and the malignant behaviors of DTX-resistant PCa cells.
Hsa_circ_0000735 downregulation boosted PCa sensitivity to DTX and reduced tumor growth via sponging miR-7, providing a promising prognostic biomarker and therapeutic target for PCa.
前列腺癌（PCa）治疗失败的主要原因之一是产生化疗耐药性。环状RNA hsa_circ_0000735（hsa_circ_0000735）与癌症进展相关。然而，hsa_circ_0000735在PCa对多西他赛（DTX）耐药中的作用及调控机制尚不清楚。
通过定量实时聚合酶链反应（qRT-PCR）检测组织样本和细胞中hsa_circ_0000735和miR-7-5p（miR-7）的表达水平。通过细胞计数试剂盒-8（CCK-8）、细胞集落形成或流式细胞术检测DTX耐药PCa细胞的DTX敏感性、活力、集落形成、细胞周期进程和凋亡。通过蛋白质印迹法检测多药耐药蛋白1（MDR1）、细胞周期蛋白D1和B细胞淋巴瘤2（bcl-2）的水平。通过双荧光素酶报告基因、RNA免疫沉淀（RIP）和RNA下拉实验验证hsa_circ_0000735与miR-7之间的相互作用。通过肿瘤形成实验验证hsa_circ_0000735在体内的作用。
在DTX耐药的PCa组织和细胞中，hsa_circ_0000735上调，miR-7下调。hsa_circ_0000735高表达者总生存期较短。hsa_circ_0000735敲低和miR-7模拟物均提高了DTX耐药PCa细胞的DTX敏感性，抑制了活力、集落形成和细胞周期进程，并促进了凋亡。此外，hsa_circ_0000735沉默提高了DTX敏感性并抑制了体内PCa肿瘤生长。机制上，hsa_circ_0000735作为miR-7的海绵。miR-7抑制逆转了hsa_circ_0000735沉默介导的对DTX敏感性和DTX耐药PCa细胞恶性行为的影响。
hsa_circ_0000735下调通过海绵吸附miR-7提高了PCa对DTX的敏感性并减少了肿瘤生长，为PCa提供了一个有前景的预后生物标志物和治疗靶点。
