敲降lncRNA UCA1降低人膀胱癌细胞系T24对吉西他滨耐药

doi:10.16352/j.issn.1001-6325.2024.08.1113

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (8): 1113-1119.doi: 10.16352/j.issn.1001-6325.2024.08.1113

敲降lncRNA UCA1降低人膀胱癌细胞系T24对吉西他滨耐药

周昌东, 林洋, 孙凯, 田玉新^*

吉林省肿瘤医院泌尿外科,长春 130012

收稿日期:2023-08-25 修回日期:2024-04-01 出版日期:2024-08-05 发布日期:2024-07-24
通讯作者: ^*xiaoxinhaidan@163.com
基金资助:
吉林省卫健委基金支持项目(2021LC126)

Knockdown of lncRNA UCA1 reduces gemcitabine resistance of human bladder cancer cell line T24

ZHOU Changdong, LIN Yang, SUN Kai, TIAN Yuxin^*

Department of Urology, Jilin Province Cancer Hospital, Changchun 130012, China

Received:2023-08-25 Revised:2024-04-01 Online:2024-08-05 Published:2024-07-24
Contact: ^*xiaoxinhaidan@163.com

摘要/Abstract

摘要： 目的探讨lncRNA UCA1对人膀胱癌细胞系T24体外对吉西他滨(GEM)耐药的影响及相关分子机制。方法用RT-qPCR检测T24细胞和T24/GEM细胞中UCA1 mRNA表达。用不同浓度GEM(0.1、1和10 μmol/L)刺激T24/GEM细胞48 h,用LC3染色法观察自噬斑,Western blot检测自噬相关蛋白质表达。将UCA1-shRNA或UCA1-shRNA+pcDNA-Bcl-2转入T24/GEM细胞,用MTT法和流式细胞测量术评估细胞对GEM的敏感性;用Western blot检测p53、Bcl-2和自噬相关蛋白质的表达。结果 T24/GEM细胞中UCA1的表达显著高于亲本T24细胞(P＜0.05)。在0~10 μmol/L浓度范围的GEM呈依赖性促进T24/GEM细胞自噬(P＜0.05)。敲降UCA1后,T24/GEM细胞对GEM的敏感性增加(P＜0.05),自噬能力减弱(P＜0.05),p53和Bcl-2表达降低(P＜0.05)。Bcl-2过表达能部分逆转UCA1-shRNA对T24/GEM细胞的GEM增敏和抑制自噬的作用(P＜0.05)。结论敲降lncRNA UCA1通过抑制Bcl-2介导的自噬降低T24/GEM细胞对GEM的耐药性。

关键词: 膀胱癌, lncRNA UCA1, Bcl-2, 自噬, 吉西他滨

Abstract: Objective To investigate the in vitro effect of lncRNA UCA1 on gemcitabine (GEM) resistance of bladder cancer cell line T24 and its related molecular mechanism. Methods The mRNA expression of UCA1 in T24 cells and in T24/GEM cells was detected by RT-qPCR. The T24/GEM cells were incubated with varying concentrations (0.1, 1, and 10 μmol/L) of GEM for 48 hrs. LC3 staining microscopy was employed to visualize autophagic puncta, while the expression of autophagy-related proteins was assessed by Western blot. UCA1-shRNA and UCA1-shRNA+ pcDNA-Bcl-2 were transferred into T24/GEM cells, the sensitivity of cells to GEM was evaluated by MTT method and flow cytometry; the expressions of p53 and Bcl-2 were detected by Western blot. Results The expression level of UCA1 in T24/GEM cells was significantly higher than that of parental T24 cells (P＜0.05). The concentration of GEM in the range of 0-10 μmol/L significantly induced dose-dependent autophagy in T24/GEM cells (P＜0.05). Knockdown of UCA1 enhanced the sensitivity of T24/GEM cells to GEM (P＜0.05), while reducing autophagy (P＜0.05) and down-regulating the expression of p53 and Bcl-2(P＜0.05). Over-expression of Bcl-2 partially reversed the GEM sensitization and autophagy inhibition of UCA1-shRNA in T24/GEM cells (P＜0.05). Conclusions Knockdown of lncRNA UCA1 reduces GEM resistance of T24/GEM cells by inhibiting Bcl-2 mediated autophagy.

Key words: bladder cancer, lncRNA UCA1, Bcl-2, autophagy, gemcitabine

中图分类号:

R737.1

周昌东, 林洋, 孙凯, 田玉新. 敲降lncRNA UCA1降低人膀胱癌细胞系T24对吉西他滨耐药[J]. 基础医学与临床, 2024, 44(8): 1113-1119.

ZHOU Changdong, LIN Yang, SUN Kai, TIAN Yuxin. Knockdown of lncRNA UCA1 reduces gemcitabine resistance of human bladder cancer cell line T24[J]. Basic & Clinical Medicine, 2024, 44(8): 1113-1119.

参考文献

[1] Richters A, Aben KKH, Kiemeney LALM. The global burden of urinary bladder cancer: an update[J]. World J Urol, 2020, 38:1895-1904.
[2] Tian YQ, Yang JC, Hu JJ, et al. Trends and risk factors of global incidence, mortality, and disability of genitourinary cancers from 1990 to 2019: systematic analysis for the global burden of disease study 2019[J]. Front Public Health, 2023, 11:1119374. doi: 10.3389/fpubh.2023.1119374.
[3] Patel VG, Oh WK, Galsky MD. Treatment of muscle-invasive and advanced bladder cancer in 2020[J]. CA Cancer J Clin, 2020, 70:404-423.
[4] Pfister C, Gravis G, Fléchon A, et al. Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin or gemcitabine and cisplatin as perioperative chemotherapy for patients with nonmetastatic muscle-invasive bladder cancer: results of the GETUG-AFU V05 VESPER Trial[J]. J Clin Oncol, 2022, 40:2013-2022.
[5] Li Z, Niu H, Qin Q, et al. lncRNA UCA1 mediates resistance to cisplatin by regulating the miR-143/FOSL2-signaling pathway in ovarian cancer[J]. Mol Ther Nucleic Acids, 2019, 17:92-101.
[6] Bian Z, Jin L, Zhang J, et al. LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p[J]. Sci Rep, 2016, 6:23892. doi: 10.1038/srep23892.
[7] Shang C, Guo Y, Zhang J, et al. Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer[J]. Cancer Chemother Pharmacol, 2016, 77:1061-1067.
[8] Fang Q, Chen X, Zhi X. Long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) increases multi-drug resistance of gastric cancer via downregulating miR-27b[J]. Med Sci Monit, 2016, 22:3506-3513.
[9] Bashiri H, Tabatabaeian H. Autophagy: a potential therapeutic target to tackle drug resistance in multiple myeloma[J]. Int J Mol Sci, 2023, 24:6019. doi: 10.3390/ijms24076019.
[10] Li C, Zhao Z, Zhou Z, et al. Linc-ROR confers gemcitabine resistance to pancreatic cancer cells via inducing autophagy and modulating the miR-124/PTBP1/PKM2 axis[J]. Cancer Chemother Pharmacol, 2016, 78:1199-1207.
[11] Hu Z, Cai M, Zhang Y, et al. miR-29c-3p inhibits autophagy and cisplatin resistance in ovarian cancer by regulating FOXP1/ATG14 pathway[J]. Cell Cycle, 2020, 19:193-206.
[12] Azhati B, Maolakuerban N, Ma T, et al. Up-regulation of DRAM2 promotes tolerance of bladder transitional cell carcinoma to gemcitabine[J]. Arch Med Sci, 2020, 16:1207-1217.
[13] Li Z, Song Y, Hou W, et al. Atractylodin induces oxidative stress-mediated apoptosis and autophagy in human breast cancer MCF-7 cells through inhibition of the P13K/Akt/mTOR pathway[J]. J Biochem Mol Toxicol, 2022, 36:e23081. doi: 10.1002/jbt.23081.
[14] Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer[J]. Mol Cancer, 2020, 19:12. doi: 10.1186/s12943-020-1138-4.

[1]	张祥鑫, 李文. 线粒体自噬在肝脏缺血再灌注损伤中的作用[J]. 基础医学与临床, 2024, 44(6): 877-881.
[2]	张玉苓, 张珂, 许艇, 张庆. 胎儿生长受限孕妇胎盘自噬相关蛋白表达水平及其临床意义[J]. 基础医学与临床, 2024, 44(4): 528-532.
[3]	杨铠菲, 朱静格, 张洋洋, 赵俊果, 高雨悦, 胡焕焕, 姬国杰. 索拉菲尼诱导的细胞凋亡和自噬对HeLa细胞耐药性的影响[J]. 基础医学与临床, 2024, 44(4): 467-473.
[4]	李庆菊, 于然, 陈佳佳, 陈皓瑜, 宋坚, 王万鹏. 雷帕霉素减轻碘佛醇诱导的模型大鼠急性肾损伤[J]. 基础医学与临床, 2024, 44(1): 31-36.
[5]	徐桂萍, 陈雪莹, 张宇轩, 麦丽帕特·伊力艾克拜尔. 利多卡因对急性肺损伤模型大鼠肺组织线粒体自噬的影响[J]. 基础医学与临床, 2023, 43(9): 1394-1398.
[6]	李想, 李晔. 非酒精性脂肪性肝病中自噬与铁死亡相互作用的研究进展[J]. 基础医学与临床, 2023, 43(8): 1294-1298.
[7]	张培波, 李义. 沙棘总黄酮抑制膀胱癌细胞系T24增殖[J]. 基础医学与临床, 2023, 43(7): 1122-1126.
[8]	马聪聪, 刘洋, 吕洋, 王海萍. 线粒体自噬在心肌缺血/再灌注损伤中的作用研究进展[J]. 基础医学与临床, 2023, 43(11): 1723-1727.
[9]	贾楠, 王志莲. CALCOCO1与恶性肿瘤的发生发展[J]. 基础医学与临床, 2023, 43(11): 1733-1737.
[10]	高朋, 徐丹丹, 张斌, 刘训涛, 舒丽莎. 氯喹对人宫颈癌细胞系HeLa增殖、凋亡及自噬的影响[J]. 基础医学与临床, 2023, 43(10): 1512-1517.
[11]	付士祥, 席月, 丁龙坤, 闫曼, 赵俊, 焦玉东, 吴亮. 鲍曼不动杆菌外膜囊泡诱发人单核-巨噬细胞THP-1的炎性反应[J]. 基础医学与临床, 2023, 43(1): 110-115.
[12]	董军立, 蔡少康, 严蕾, 蔡毅. 二甲双胍抑制腰椎间盘退变模型兔椎间盘组织的细胞凋亡[J]. 基础医学与临床, 2023, 43(1): 116-122.
[13]	郑研, 李岚, 高秋英, 牛奔, 张维华. 上调miR-140增强人CML细胞株KBM5R对伊马提尼的敏感性[J]. 基础医学与临床, 2022, 42(9): 1344-1349.
[14]	白冰, 张海芳, 杨庆良, 秦悦, 周晨龙, 宋歌, 王颖. 下调lncRNA RHPN1-AS1抑制人膀胱癌细胞系T24增殖和迁移[J]. 基础医学与临床, 2022, 42(6): 940-944.
[15]	黄云, 许喜生, 陈凯, 何秀. 下调lncRNA-H19表达促进人瘢痕疙瘩成纤维细胞凋亡和自噬[J]. 基础医学与临床, 2022, 42(4): 633-639.

敲降lncRNA UCA1降低人膀胱癌细胞系T24对吉西他滨耐药

Knockdown of lncRNA UCA1 reduces gemcitabine resistance of human bladder cancer cell line T24

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价