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低表达 LncRNA ZNF667-AS1 是宫颈癌的独立预后因素,对宫颈癌的增殖具有抑制作用。

Independent prognostic Factor of low-expressed LncRNA ZNF667-AS1 for cervical cancer and inhibitory function on the proliferation of cervical cancer.

机构信息

Department of Obstetrics and Gynecology, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5353-5360. doi: 10.26355/eurrev_201712_13920.

DOI:10.26355/eurrev_201712_13920
PMID:29243775
Abstract

OBJECTIVE

To investigate the expression of long non-coding RNA ZNF667-AS1 in cervical cancer and its effect on the proliferation of cervical cancer cell line, SiHa cells.

MATERIALS AND METHODS

The expression level of ZNF667-AS1 from two microarray datasets (GSE63514 and GSE6791) and TCGA (The Cancer Genome Atlas) were selected to analyze the difference between cervical cancer tissues and normal cervical tissues with bioinformatics methods. Then, the prognosis of ZNF667-AS1 was calculated in TCGA. The expression of LncRNA ZNF667-AS1 in 30 normal cervical tissues and 60 cervical cancer tissue samples was explored using qRT-PCR. In addition, analysis of the clinical data found that the expression of LncRNA ZNF667-AS1 was correlated with the total survival, tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage. At last, the proliferative ability was detected by CCK8 and colon formation assay.

RESULTS

Search the relevant microarray datasets using the keywords "cervical cancer" and "GPL570" from the Gene Expression Omnibus (GEO) database. Afterwards, two microarray datasets (GSE63514 and GSE6791) were selected to analyze the differentially expressed genes in cervical cancer tissues and normal cervical tissues using bioinformatics methods. The results showed that the expression of LncRNA ZNF667-AS1 in cervical cancer was significantly lower than that in normal cervical tissues. 30 normal cervical tissues and 60 cervical cancer tissue samples were selected to extract total RNA for qRT-PCR experiment, and found that the expression of LncRNA ZNF667-AS1 in cervical cancer tissues was lower than that in normal cervical tissues, which was consistent with that of TCGA. Analysis of the clinical data found that the expression of LncRNA ZNF667-AS1 was correlated with the total survival, tumor size and FIGO stage. Compared with the negative control group, the proliferation ability and cell cloning ability of cells with over-expressed LncRNA ZNF667-AS1 were significantly decreased (p<0.001), indicating that overexpression of ZNF667-AS1 inhibited the proliferation of SiHa cells.

CONCLUSIONS

Expression of LncRNA ZNF667-AS1 was significantly lower in cervical cancer tissues, and its expression was negatively correlated with the overall survival, tumor size and FIGO stage. ZNF667-AS1 inhibited the proliferation of cervical cancer cells and was expected to be the biomarker and potential therapeutic target for predicting cervical cancer and determining its prognosis.

摘要

目的

研究长链非编码 RNA ZNF667-AS1 在宫颈癌中的表达及其对宫颈癌 SiHa 细胞增殖的影响。

材料与方法

通过生物信息学方法,从两个基因芯片数据集(GSE63514 和 GSE6791)和 TCGA(癌症基因组图谱)中选择 ZNF667-AS1 的表达水平,分析宫颈癌组织与正常宫颈组织之间的差异。然后,在 TCGA 中计算 ZNF667-AS1 的预后。采用 qRT-PCR 法检测 30 例正常宫颈组织和 60 例宫颈癌组织样本中 LncRNA ZNF667-AS1 的表达。此外,分析临床资料发现,LncRNA ZNF667-AS1 的表达与总生存、肿瘤大小和国际妇产科联合会(FIGO)分期相关。最后,通过 CCK8 和克隆形成实验检测增殖能力。

结果

从基因表达综合数据库(GEO)中使用“宫颈癌”和“GPL570”关键词搜索相关基因芯片数据集,选择两个基因芯片数据集(GSE63514 和 GSE6791),通过生物信息学方法分析宫颈癌组织与正常宫颈组织中差异表达基因。结果显示,LncRNA ZNF667-AS1 在宫颈癌组织中的表达明显低于正常宫颈组织。选择 30 例正常宫颈组织和 60 例宫颈癌组织标本提取总 RNA 进行 qRT-PCR 实验,发现宫颈癌组织中 LncRNA ZNF667-AS1 的表达低于正常宫颈组织,与 TCGA 结果一致。分析临床资料发现,LncRNA ZNF667-AS1 的表达与总生存、肿瘤大小和 FIGO 分期相关。与阴性对照组相比,过表达 LncRNA ZNF667-AS1 的细胞增殖能力和细胞克隆能力明显降低(p<0.001),表明 ZNF667-AS1 过表达抑制了 SiHa 细胞的增殖。

结论

LncRNA ZNF667-AS1 在宫颈癌组织中的表达明显降低,其表达与总生存、肿瘤大小和 FIGO 分期呈负相关。ZNF667-AS1 抑制宫颈癌细胞的增殖,有望成为预测宫颈癌和判断其预后的生物标志物和潜在治疗靶点。

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