Cui LiJuan, Nai ManMan, Zhang Ke, Li Lu, Li RuiMin
Department of Gynecology, First People's Hospital of Jiaozuo City, Jiaozuo, Henan Province, China,
Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Cancer Manag Res. 2019 Jan 11;11:651-667. doi: 10.2147/CMAR.S176525. eCollection 2019.
Emerging evidences have demonstrated that lncRNAs play vital roles in various pathological processes, including cancer. The lncRNA WT1 antisense RNA (WT1-AS) serves as a tumor suppressor in various cancers. Nevertheless, the expression and precise function of WT1-AS in cervical carcinoma still remain not yet investigated. The objective of our study was to explore the expression of WT1-AS and its biological roles in cervical cancer.
Differences in the lncRNA expression profiles between cervical cancer and adjacent normal tissues were assessed by lncRNA expression microarray analysis. The expression of p53 in cervical cancer cell was assessed by qRT-PCR and immunofluorescence assay. Loss-of-function studies were used to explore the effect of lncRNA WT1-AS on the growth and metastasis of cervical cancer cell in vitro and in vivo.
Our results demonstrated that WT1-AS was remarkably down-regulated in cervical carcinoma. Functional assays proved that up-regulation of WT1-AS significantly suppressed cervical cancer cell proliferation, migration and invasion. In addition, the luciferase reporter assay identified that miR-330-5p was the target of WT1-AS. Moreover, tumor suppressor p53 was identified as the direct target of miR-330-5p and alternation of miR-330-5p/p53 axis reversed the effects of WT1-AS in cervical cancer cell.
Altogether, our findings suggested that WT1-AS was down-regulated in cervical carcinoma and WT1-AS suppressed cervical carcinoma cell- proliferation, migration and invasion through regulating the miR-330-5p/p53 axis.
新出现的证据表明,长链非编码RNA(lncRNA)在包括癌症在内的各种病理过程中发挥着至关重要的作用。lncRNA WT1反义RNA(WT1-AS)在多种癌症中作为肿瘤抑制因子。然而,WT1-AS在宫颈癌中的表达及确切功能仍未得到研究。我们研究的目的是探讨WT1-AS在宫颈癌中的表达及其生物学作用。
通过lncRNA表达微阵列分析评估宫颈癌组织与相邻正常组织之间lncRNA表达谱的差异。采用qRT-PCR和免疫荧光测定法评估宫颈癌细胞中p53的表达。通过功能缺失研究探讨lncRNA WT1-AS对宫颈癌细胞体外和体内生长及转移的影响。
我们的结果表明,WT1-AS在宫颈癌中显著下调。功能分析证明,WT1-AS的上调显著抑制宫颈癌细胞的增殖、迁移和侵袭。此外,荧光素酶报告基因检测确定miR-330-5p是WT1-AS的靶标。此外,肿瘤抑制因子p53被确定为miR-330-5p的直接靶标,miR-330-5p/p53轴的改变逆转了WT1-AS对宫颈癌细胞的影响。
总之,我们的研究结果表明,WT1-AS在宫颈癌中表达下调,且WT1-AS通过调节miR-330-5p/p53轴抑制宫颈癌细胞的增殖、迁移和侵袭。