Xie Fang, Zhao Ning, Zhang Hui, Xie Dalong
Medical Basic Experimental Teaching Center, China Medical University, Shenyang, 110122, China.
Surgery Laboratory, Affiliated First Hospital, China Medical University, Shenyang, 110001, China.
J Cancer. 2020 Jan 22;11(7):1907-1912. doi: 10.7150/jca.39722. eCollection 2020.
: Recent studies showed circular RNA (circRNA) played important regulatory roles in tumors, including genesis of chemotherapy resistance. In this study, the role of circHIPK3 on chemotherapy resistance of bladder cancer (BC) will be clarified. : Real-time quantitative PCR was applied to examine the circHIPK3 expression. The gemcitabine sensitivity and cell proliferation viability were analyzed by Cell Counting Kit-8 assay. Double-stained flow cytometry was used to detect the cell apoptosis. : In BC tissues and cell lines, the circHIPK3 expression was down-regulated. Its expression had a negative correlation with pathological grade, lymph node metastasis and gemcitabine insensitivity of BC patients. CircHIPK3 was a independent prognostic biomarker for BC patients. The expression of circHIPK3 in T24/gem and J82/gem cell lines (resistant to gemcitabine) was down-regulated significantly. The over-expression of circHIPK3 decreased IC50 of gemcitabine and promoted gemcitabine's cytotoxicity in T24/gem and J82/gem cells. : The circHIPK3 is low-expressed in BC and is an independent prognostic biomarker for BC patients. The low-expression of circHIPK3 is associated with the insensitivity to gemcitabine of BC patients, over-expression of circHIPK3 promotes gemcitabine sensitivity in BC.
近期研究表明,环状RNA(circRNA)在肿瘤中发挥重要调控作用,包括化疗耐药的发生。在本研究中,将阐明circHIPK3在膀胱癌(BC)化疗耐药中的作用。
采用实时定量PCR检测circHIPK3表达。通过细胞计数试剂盒-8法分析吉西他滨敏感性和细胞增殖活力。采用双染流式细胞术检测细胞凋亡。
在BC组织和细胞系中,circHIPK3表达下调。其表达与BC患者的病理分级、淋巴结转移和吉西他滨不敏感性呈负相关。circHIPK3是BC患者的独立预后生物标志物。circHIPK3在T24/gem和J82/gem细胞系(对吉西他滨耐药)中的表达显著下调。circHIPK3的过表达降低了吉西他滨的半数抑制浓度(IC50),并增强了吉西他滨在T24/gem和J82/gem细胞中的细胞毒性。
circHIPK3在BC中低表达,是BC患者的独立预后生物标志物。circHIPK3的低表达与BC患者对吉西他滨的不敏感性相关,circHIPK3的过表达可提高BC对吉西他滨的敏感性。