Effect of lncRNA PANDAR on Cisplatin chemosensitivity of cervical cancer cells and Cisplatin-resistant cells
ZHU Qian1,2 ZHANG Ling3 YUAN Peng2 LI Yu4 ZHANG Wei1 YANG Hong1
1.Department of Gynecology, Xijing Hospital, the First Affiliated Hospital of Air Force Military Medical University, Shaanxi Province, Xi′an 710032, China;
2.Ward One, Department of Gynecology, Northwest Women′s and Children′s Hospital, Shaanxi Province, Xi′an 710032, China;
3.Department of Gynecology and Endocrinology, Northwest Women′s and Children′s Hospital, Shaanxi Province, Xi′an 710032, China;
4.Department of Biochemical Teaching and Research of Air Force Military Medical University, Shaanxi Province, Xi′an 710032, China
Abstract:Objective To explore the effect of lncRNA PANDAR on the resistance and sensitivity of Cisplatin in cervical cancer cells. Methods Human cervical cancer Cisplatin-resistant cells named HeLa-DDP were constructed. The parent HeLa and HeLa-DDP cells were stimulated with 1, 2, 4, 8, 16 μg/mL doses of Cisplatin. The recombinant PANDAR vectors or lentiviral plasmid of sh-PANDAR were transfected into HeLa-DDP and HeLa cells. All cells were divided into different groups: control group, vector group, PANDAR group, sh-NC group and sh-PANDAR group. Then, PANDAR expression was detected by qRT-PCR. CCK-8 assay was conducted to determine cell viability. Cell apoptosis was analyzed by flow cytometry. Results HeLa-DDP cells exhibited stronger resistance to Cisplatin relative to parent HeLa cells (P < 0.05). In contrast to parent HeLa cells, PANDAR expression was decreased in HeLa-DDP cells (P < 0.05). Overexpression of PANDAR inhibited cell viability under Cisplatin exposure in HeLa-DDP cells relative to control groups (P < 0.05), concomitant with increases in cell apoptosis (P < 0.05). Whilst, PANDAR cessation enhanced cell viability in HeLa-DDP cells under Cisplatin exposure (P < 0.05). Additionally, PANDAR knockdown increased HeLa cell viability upon Cisplatin conditions (P < 0.05). Conclusion PANDAR may regulate cell resistance to Cisplatin in HeLa-DDP and HeLa cells.
[1] Torre LA,Islami F,Siegel RL,et al. Global Cancer in Women:Burden and Trends [J]. Cancer Epidemiol Biomarkers Prev,2017,26(4):444-457.
[2] Allemani C,Weir HK,Carreira H,et al. Global surveillance of cancer survival 1995-2009:analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2) [J]. Lancet,2015, 385(9972):977-1010.
[3] Kumar L,Harish P,Malik PS,et al. Chemotherapy and targeted therapy in the management of cervical cancer [J]. Curr Probl Cancer,2018,42(2):120-128.
[4] Espina M,Corte-Rodriguez M,Aguado L,et al. Cisplatin resistance in cell models:evaluation of metallomic and biological predictive biomarkers to address early therapy failure [J]. Metallomics,2017,9(5):564-574.
[5] 刘红,张国楠.宫颈癌化疗耐药相关问题[J].中国实用妇科与产科杂志,2015,31(3):198-201.
[6] 刘宁,成冬冬,姜金波.长链非编码RNA PANDAR促进结直肠癌转移的作用和机制研究[J].中国癌症杂志,2017,27(4):268-275.
[7] Ma PJ,Guan QK,Xu DW,et al. LncRNA PANDAR as a prognostic marker in Chinese cancer [J]. Clin Chim Acta,2017,475:172-177.
[8] Liu J,Ben Q,Lu E,et al. Long noncoding RNA PANDAR blocks CDKN1A gene transcription by competitive interaction with p53 protein in gastric cance [J]. Cell Death Dis,2018,9(2):168.
[9] Zhu H,Luo H,Zhang W,et al. Molecular mechanisms of Cisplatin resistance in cervical cancer [J]. Drug Des Devel Ther,2016,10:1885-1895.
[10] Bhan A,Soleimani M,Mandal SS. Long Noncoding RNA and Cancer:A New Paradigm [J]. Cancer Res,2017,77(15):3965-3981.
[11] Ma Y,Zhang J,Wen L,et al. Membrane-lipid associated lncRNA:A new regulator in cancer signaling [J]. Cancer Lett,2018,419:27-29.
[12] Renganathan A,Felley-Bosco E. Long Noncoding RNAs in Cancer and Therapeutic Potential [J]. Adv Exp Med Biol,2017,1008:199-222.
[13] Cai Z,Xu K,Li Y,et al. Long noncoding RNA in liver cancer stem cells [J]. Discov Med,2017,24(131):87-93.
[14] Momen-Heravi F,Bala S. Emerging role of non-coding RNA in oral cancer [J]. Cell Signal,2018,42:134-143.
[15] Dasari S,Tchounwou PB. Cisplatin in cancer therapy:molecular mechanisms of action [J]. Eur J Pharmacol,2014,740:364-378.
[16] Rivandi M,Pasdar A,Hamzezadeh L,et al. The prognostic and therapeutic values of long noncoding RNA PANDAR in colorectal cancer [J]. J Cell Physiol,2019,234(2):1230-1236.
[17] Yang L,Zhou JD,Zhang TJ,et al. Overexpression of lncRNA PANDAR predicts adverse prognosis in acute myeloid leukemia [J]. Cancer Manag Res,2018,10:4999-5007.
[18] Huang HW,Xie H,Ma X,et al. Upregulation of LncRNA PANDAR predicts poor prognosis and promotes cell proliferation in cervical cancer [J]. Eur Rev Med Pharmacol Sci,2017,21(20):4529-4535.
[19] Zou Y,Zhong Y,Wu J,et al. Long non-coding PANDAR as a novel biomarker in human cancer:A systematic review [J]. Cell Prolif,2018,51(Suppl 7):e12422.
[20] Zhan Y,Lin J,Liu Y,et al. Up-regulation of long non-coding RNA PANDAR is associated with poor prognosis and promotes tumorigenesis in bladder cancer [J]. J Exp Clin Cancer Res,2016,35(1):83.
[21] Wang H,Fang L,Jiang J,et al. The Cisplatin-induced lncRNA PANDAR dictates the chemoresistance of ovarian cancer via regulating SFRS2-mediated p53 phosphorylation [J]. Cell Death Dis,2018,9(11):1103.