Ding Yuansheng, Li Xiaoyan, Zhang Yucui, Zhang Jie
The First Department of General Surgery, Linyi Central Hospital, Linyi 276400, Shandong Province, People's Republic of China.
Cancer Manag Res. 2020 Feb 20;12:1281-1292. doi: 10.2147/CMAR.S234620. eCollection 2020.
Emerging studies have reported that long non-coding RNAs (lncRNAs) were crucial regulators in the progression of colorectal cancer (CRC). LncRNA susceptibility 9 (CASC9) was involved in several cancers; however, its role in CRC remains unknown.
RT-PCR was done to probe the expression of CASC9 and miR-193a-5p in CRC samples. CRC cell lines (HCT116 and SW480) were used as cell models. The biological influence of CASC9 on cancer cells was studied using CCK-8 assay, Transwell assay and TUNEL assay in vitro, and subcutaneous xenotransplanted tumor model in vivo. Interaction between CASC9 and miR-193a-5p was investigated by bioinformatics analysis, RT-PCR, and luciferase reporter assay. The expression level of the downstream gene of miR-193a-5p, erb-b2 receptor tyrosine kinase 2 (ERBB2), was tested by Western blot.
CASC9 was significantly up-regulated in CRC samples, while miR-193a-5p was markedly down-regulated. Overexpression of CASC9 promoted viability, migration and invasion of CRC cells, while overexpression of miR-193a-5p had the opposite effect. CASC9 could down-regulate miR-193a-5p via sponging it, and there was a negative relevancy between CASC9 and miR-193a-5p in CRC samples. CASC9 also enhanced the expression levels of ERBB2, while this effect could be reversed by co-transfection with miR-193a-5p.
CASC9, an oncogenic lncRNA, was abnormally up-regulated in CRC tissues, and it could indirectly modulate the expression of ERBB2 via reducing the expression level of miR-193a-5p.
新兴研究报道长链非编码RNA(lncRNAs)是结直肠癌(CRC)进展中的关键调节因子。LncRNA易感性9(CASC9)与多种癌症有关;然而,其在CRC中的作用尚不清楚。
采用逆转录聚合酶链反应(RT-PCR)检测CRC样本中CASC9和miR-193a-5p的表达。使用CRC细胞系(HCT116和SW480)作为细胞模型。通过体外CCK-8检测、Transwell检测和TUNEL检测以及体内皮下异种移植肿瘤模型研究CASC9对癌细胞的生物学影响。通过生物信息学分析、RT-PCR和荧光素酶报告基因检测研究CASC9与miR-193a-5p之间的相互作用。通过蛋白质免疫印迹法检测miR-193a-5p下游基因erb-b2受体酪氨酸激酶2(ERBB2)的表达水平。
CASC9在CRC样本中显著上调,而miR-193a-5p明显下调。CASC9的过表达促进了CRC细胞的活力、迁移和侵袭,而miR-193a-5p的过表达则产生相反的效果。CASC9可通过海绵吸附作用下调miR-193a-5p,且CRC样本中CASC9与miR-193a-5p之间存在负相关性。CASC9还增强了ERBB2的表达水平,而与miR-193a-5p共转染可逆转这种作用。
CASC9是一种致癌lncRNA,在CRC组织中异常上调,它可通过降低miR-193a-5p的表达水平间接调节ERBB2的表达。