长链非编码 RNA BLACAT1 通过激活 Wnt/β-连环蛋白信号通路促进宫颈癌中的细胞增殖、迁移和侵袭。
Long non-coding RNA BLACAT1 promotes cell proliferation, migration and invasion in cervical cancer through activation of Wnt/β-catenin signaling pathway.
机构信息
Regular Physical Examination Centre, Department of Gynecology, Weifang Municipal Official Hospital, Weifang, Shandong, China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 May;22(10):3002-3009. doi: 10.26355/eurrev_201805_15057.
OBJECTIVE
Long noncoding RNAs (lncRNAs) are aberrantly expressed in various cancers. The purpose of this study was to determine the association of lncRNA (BLACAT1) with the prognosis of cervical cancer (CC) patients, and to further investigate the potential mechanisms of BLACAT1 function in CC progression.
PATIENTS AND METHODS
The expressions of BLACAT1 in CC tissues and cells were estimated by quantitative Real-time polymerase chain reaction (qRT-PCR). We compared the expression of BLACAT1 with the clinicopathological characteristics and survival of CC patients. MTT, colony formation, and transwell assay were performed to explore the effects of BLACAT1 expression on growth, migration, and invasion of CC cells. Protein levels of β-catenin and MMP-7 were evaluated by Western blotting.
RESULTS
We found that BLACAT1 expression was significantly increased in CC tissues and cells lines. In addition, the expression level of BLACAT1 was positively correlated with distant metastasis (p=0.001), FIGO stage (p=0.010), and histological grade (p=0.012). Moreover, patients with high BLACAT12 expression had shorter overall survival and progression-free survival time than those with low BLACAT1 expression, with the data provided by multivariate analysis suggesting that BLACAT1 expression could serve as an independent prognostic factor in CC patients. Functionally, in vitro assay indicated that down-regulation of BLACAT1 significantly suppressed CC cells proliferation, migration, and invasion. Mechanistically, the results of Western blot showed that the expression of β-catenin and MMP-7 was significantly down-regulated in CC cells transfected with si-BLACAT1.
CONCLUSIONS
These findings suggested that BLACAT1, as a novel prognostic biomarker, might be an oncogenic lncRNA which promoted proliferation, migration, and invasion by modulating Wnt/β-catenin signaling. Our results enlarged our knowledge in the molecular pathology of CC tumorigenesis.
目的
长链非编码 RNA（lncRNA）在各种癌症中表达异常。本研究旨在确定 lncRNA（BLACAT1）与宫颈癌（CC）患者预后的关联，并进一步探讨 BLACAT1 在 CC 进展中的潜在作用机制。
方法
通过实时定量聚合酶链反应（qRT-PCR）评估 CC 组织和细胞中 BLACAT1 的表达。我们比较了 BLACAT1 的表达与 CC 患者的临床病理特征和生存情况。MTT、集落形成和 Transwell 分析用于研究 BLACAT1 表达对 CC 细胞生长、迁移和侵袭的影响。通过 Western blot 评估 β-catenin 和 MMP-7 的蛋白水平。
结果
我们发现 BLACAT1 在 CC 组织和细胞系中的表达明显增加。此外，BLACAT1 的表达水平与远处转移（p=0.001）、FIGO 分期（p=0.010）和组织学分级（p=0.012）呈正相关。此外，高 BLACAT1 表达组患者的总生存时间和无进展生存时间明显短于低 BLACAT1 表达组，多变量分析数据表明 BLACAT1 表达可作为 CC 患者的独立预后因素。功能实验表明，下调 BLACAT1 可显著抑制 CC 细胞的增殖、迁移和侵袭。机制研究表明，在转染 si-BLACAT1 的 CC 细胞中，β-catenin 和 MMP-7 的表达明显下调。
结论
这些发现表明，BLACAT1 作为一种新的预后生物标志物，可能是一种致癌的 lncRNA，通过调节 Wnt/β-catenin 信号通路促进增殖、迁移和侵袭。我们的研究结果扩大了我们对 CC 肿瘤发生分子病理学的认识。
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