Long noncoding RNA HOXD-AS1 regulates proliferation of cervical cancer cells by activating Ras/ERK signaling pathway

Long noncoding RNA HOXD-AS1 regulates proliferation of cervical cancer cells by activating Ras/ERK signaling pathway
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DOI:
10.26355/eurrev_201711_13817
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发表时间:
2017-11-01
影响因子:
3.3
通讯作者:
Liu, L. -L.
Liu, L. -L.
中科院分区:
医学4区
文献类型:
--
作者:
Hu, Y. -C.;Wang, A. -M.;Liu, L. -L.

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目的:为探讨HOXD簇反义RNA 1(HOXD-AS 1)在宫颈癌中的作用及其机制,采用实时定量聚合酶链反应(RT-qPCR)检测HOXD-AS 1在宫颈癌组织中的表达。采用χ 2检验分析HOXD-AS 1表达与临床指标的相关性。用MTT法、克隆形成实验和Western blot法检测HOXD AS 1在HeLa和CaSki细胞中的活性、集落形成能力和细胞外调节蛋白激酶1/2(ERK 1/2)的磷酸化水平。HOXD-AS 1表达与肿瘤的淋巴结转移、淋巴管浸润、淋巴结转移及复发有关。HOXD-AS 1基因敲低可显著抑制宫颈癌细胞增殖、集落形成能力和Ras/ERK信号通路。此外,异种移植实验证实了在vivo.CONCLUSIONS结果:我们的数据阐明,沉默HOXD-AS 1显着抑制细胞生长的Ras/ERK通路在宫颈癌中失活,提供了一个更详细的了解宫颈癌的发病机制,并提供了一个可能的理论基础,长非编码RNA的诊断和治疗宫颈癌。
OBJECTIVE: To investigate the effects of HOXD cluster antisense RNA 1 (HOXD-AS1) in cervical cancer and its underlying mechanism.PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of HOXD-AS1 in human cervical cancer tissues. x2-test was used for analyzing the association of HOXD-AS1 expression and clinical parameters. Cell viability, colony formation capacity, and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) in treated HeLa and CaSki cells were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, colony formation assay, and Western blot analysis, respectively.RESULTS: The results indicated that HOXD-AS1 was upregulated in cervical cancer cells significantly. Meanwhile, HOXD-AS1 expression was involved in tumor-node-metastasis stages, lymphovascular invasion, lymph node metastasis, as well as recurrence. HOXD-AS1 knockdown remarkably suppressed cervical cancer cell proliferation, colony formation capacity, and the Ras/ERK signaling pathway in vitro. Furthermore, xenograft assays confirmed the results in vivo.CONCLUSIONS: Our data elucidate that silencing HOXD-AS1 remarkably suppresses cell growth by inactivating the Ras/ERK pathway in cervical cancer, providing a more detailed understanding of cervical cancer pathogenesis and providing a possible theoretical foundation for long non-coding RNA for the diagnosis and therapy for cervical cancer.