Qiao Zhongjie, Dai Hongshuang, Zhang Yunzhu, Li Qiang, Zhao Meng, Yue Tongyun
Urology Department, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, People's Republic of China.
The 1st Nephrology Department, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, Heilongjiang 150036, People's Republic of China.
Cancer Manag Res. 2020 Mar 6;12:1661-1668. doi: 10.2147/CMAR.S223172. eCollection 2020.
Long noncoding RNAs (lncRNAs) play critical and complex roles in regulating various biological processes of cancers. Our study aimed to investigate the involvement of lncRNA NCK1-AS1 in urinary bladder cancer (UBC).
qRT-PCR was used to detect the expression of lncRNA NCK1-AS1 and miR-143 in UBC tissues and cells. The dual-luciferase reporter system assays were used to confirm the interaction between NCK1-AS1 and miR-143, and flow cytometry assays were applied to examine the behavioral changes in HT-1376 and HT-1197 cell lines.
It was observed that NCK1-AS1 was up-regulated, while miR-143 was down-regulated in tumor tissues than in adjacent healthy tissues of urinary bladder cancer (UBC) patients. A 5-year survival analysis showed that the survival rate of patients with high NCK1-AS1 level or low miR-143 level in tumor tissues appears relatively low. Correlation analysis revealed a significant inverse correlation between NCK1-AS1 and miR-143 in tumor tissues. Over-expression NCK1-AS1 reduced the expression level of miR-143, while elevating the level of miR-143 failed to affect NCK1-AS1 expression. NCK1-AS1 over-expression led to promoted proliferation and increased percentage of CD133+ (stemness) cells.
Therefore, NCK1-AS1 promotes cancer cell proliferation and increases cell stemness in UBC patients by down-regulating miR-143.
长链非编码RNA(lncRNA)在调节癌症的各种生物学过程中发挥着关键而复杂的作用。我们的研究旨在探讨lncRNA NCK1-AS1在膀胱癌(UBC)中的作用。
采用qRT-PCR检测UBC组织和细胞中lncRNA NCK1-AS1和miR-143的表达。采用双荧光素酶报告系统检测NCK1-AS1与miR-143之间的相互作用,并采用流式细胞术检测HT-1376和HT-1197细胞系的行为变化。
观察到与膀胱癌(UBC)患者的癌旁健康组织相比,肿瘤组织中NCK1-AS1上调,而miR-143下调。一项5年生存分析表明,肿瘤组织中NCK1-AS1水平高或miR-143水平低的患者生存率相对较低。相关性分析显示肿瘤组织中NCK1-AS1与miR-143之间存在显著负相关。过表达NCK1-AS1降低了miR-143的表达水平,而提高miR-143水平未能影响NCK1-AS1的表达。NCK1-AS1过表达导致细胞增殖增加和CD133+(干性)细胞百分比增加。
因此,NCK1-AS1通过下调miR-143促进UBC患者癌细胞增殖并增加细胞干性。