LncRNA ADAMTS9-AS2表达上调抑制结直肠癌的增殖和转移

Overexpression of the long non-coding RNA ADAMTS9-AS2 suppresses colorectal cancer proliferation and metastasis

目的:探讨长链非编码RNA(long non-coding RNA,lncRNA)ADAMTS9-AS2在结直肠癌(colorectal cancer,CRC)中的表达、临床意义和生物学作用。方法:利用基因芯片数据分析CRC中ADAMTS9-AS2的表达情况,并利用real-time PCR技术在20例CRC组织和癌旁正常组织及细胞系中进行验证。利用基因芯片提供的临床数据进行临床病理特征相关性分析、Kaplan-Meier生存分析和Cox回归分析。利用CCK-8、克隆形成和Transwell迁移和侵袭实验检测ADAMTS9-AS2对CRC细胞增殖、迁移和侵袭能力的影响。结果:ADAMTS9-AS2在CRC组织和细胞中显著低表达(P<0.05),其表达高低与早期CRC患者的年龄、性别、分期、病灶位置和错配修复状态均无明显相关性(P>0.05)。在早期CRC患者中,ADAMTS9-AS2高表达组患者的5年无复发生存率高于低表达组(83.8%vs 73.5%,P=0.041),ADAMTS9-AS2高表达是CRC患者无复发生存的独立保护因素(风险比=0.528,95%CI:0.299~0.932;P=0.028)。ADAMTS9-AS2表达上调能明显抑制CRC细胞的增殖和转移(P<0.05),表达下调则导致相反的结果(P<0.05)。结论:ADAMTS9-AS2通过抑制CRC细胞的增殖和转移发挥抑癌基因的作用,是CRC重要的预后因素。

Objective:To investigate the expression,clinical significance,and biological function of the long non-coding RNA(lncRNA)ADAMTS9-AS2 in colorectal cancer(CRC).Methods:Gene microarray analysis was performed to explore the expression of ADAMTS9-AS2 in CRC.Real-time PCR was used to verify its expression in 20-paired CRC tissues and adjacent non-tumor tissues.We further explored the relationship between ADAMTS9-AS2 expression and clinicopathological features,and its prognostic role in relapse-free survival(RFS)among early stage CRC patients using Kaplan-Meier and Cox regression analyses.In vitro assays,cell counting kit-8 assay,colony formation assay,and Transwell assay were used to evaluate the biological function of ADAMTS9-AS2 in CRC.Results:ADAMTS9-AS2 was down-regulated in CRC patients according to the gene microarray analysis,which was confirmed in CRC tissues and cells.High expression of ADAMTS9-AS2 was associated with a higher 5-year RFS rate(83.8%vs 73.5%,P=0.041)and it was an independent prognostic factor for RFS[hazard ratio(HR)=0.528;95%CI 0.299 to 0.932;P=0.028]at the early stage of CRC.ADAMTS9-AS2 overexpression in CRC cells inhibited cell proliferation,migration,and invasion,while suppression of ADAMTS9-AS2 showed opposite effects.Conclusion:ADAMTS9-AS2 is a valuable prognostic factor for CRC and may function as a tumor suppressor in CRC via inhibiting cell proliferation and metastasis.