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KCNMA1反义链1可减轻上皮性卵巢癌细胞的凋亡,并作为上皮性卵巢癌预后不良的一个危险因素。

KCNMA1-AS1 attenuates apoptosis of epithelial ovarian cancer cells and serves as a risk factor for poor prognosis of epithelial ovarian cancer.

作者信息

Ma S-Y, Wei P, Qu F

机构信息

Clinical Experimental Teaching Center/Department of Obstetrics and Gynecology, The First Affiliated Hospital/School of General Medicine of Xi'an Medical Universi-ty Xi'an, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Jun;23(11):4629-4641. doi: 10.26355/eurrev_201906_18041.

Abstract

OBJECTIVE

To explore the role of KCNMA1-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism.

PATIENTS AND METHODS

We first screened out the differentially expressed lncRNAs (KCNMA1-AS1) in the GEO (gene expression omnibus) database. The relationship between KCNMA1-AS1 expression and prognosis of EOC with different pathological types was analyzed by meta-analysis. Subsequently, KCNMA1-AS1 expressions in EOC tissues and normal ovarian tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between KCNMA1-AS1 level with progression-free survival (PFS) and overall survival (OS) of EOC was analyzed. Furthermore, proliferation and migration of EOC cells transfected with the corresponding plasmids were analyzed by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Apoptosis-related genes in EOC cells were detected by Western blot.

RESULTS

KCNMA1-AS1 was a risk factor for prognosis in high-grade, advanced and serous EOC. Upregulated KCNMA1-AS1 was found in EOC tissues than that of normal tissues, showing the diagnostic potential of KCNMA1-AS1 in EOC. Statistical analysis indicated that KCNMA1-AS1 was not correlated with the DFS, OS, age, histological type, lymph node metastasis and recurrence, but related to FIGO stage of EOC patients. For in vitro experiments, the proliferation and migration of were enhanced, and apoptosis of HO8910 cells overexpressing KCNMA1-AS1 was inhibited. Furthermore, elevated expressions of Caspase-3 and Caspase-9, as well as reduced expression of Bcl-xL, were observed after KCNMA1-AS1 knockdown in EOC cells.

CONCLUSIONS

KCNMA1-AS1 is overexpressed in EOC and negatively correlated with its prognosis. KCNMA1-AS1 participates in the occurrence and development of EOC by promoting proliferation, migration and inhibiting apoptosis of ovarian cancer cells via apoptosis pathway.

摘要

目的

探讨KCNMA1-AS1在上皮性卵巢癌(EOC)中的作用及其潜在机制。

患者与方法

我们首先在基因表达综合数据库(GEO)中筛选出差异表达的长链非编码RNA(lncRNA,即KCNMA1-AS1)。通过荟萃分析分析KCNMA1-AS1表达与不同病理类型EOC预后之间的关系。随后,采用定量实时聚合酶链反应(qRT-PCR)检测EOC组织和正常卵巢组织中KCNMA1-AS1的表达。分析KCNMA1-AS1水平与EOC无进展生存期(PFS)和总生存期(OS)之间的相关性。此外,分别采用细胞计数试剂盒-8(CCK-8)和Transwell实验分析转染相应质粒的EOC细胞的增殖和迁移情况。通过蛋白质免疫印迹法检测EOC细胞中凋亡相关基因。

结果

KCNMA1-AS1是高级别、晚期和浆液性EOC预后的危险因素。EOC组织中KCNMA1-AS1的表达高于正常组织,表明KCNMA1-AS1在EOC中具有诊断潜力。统计分析表明,KCNMA1-AS1与EOC患者的无病生存期(DFS)、总生存期(OS)、年龄、组织学类型、淋巴结转移和复发均无相关性,但与EOC患者的国际妇产科联盟(FIGO)分期有关。在体外实验中,过表达KCNMA1-AS1的HO8910细胞的增殖和迁移增强,凋亡受到抑制。此外,在EOC细胞中敲低KCNMA1-AS1后,观察到半胱天冬酶-3(Caspase-3)和半胱天冬酶-9(Caspase-9)的表达升高,以及Bcl-xL的表达降低。

结论

KCNMA1-AS1在EOC中过表达,且与其预后呈负相关。KCNMA1-AS1通过凋亡途径促进卵巢癌细胞的增殖、迁移并抑制其凋亡,从而参与EOC的发生发展。

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