Kim Hee Jung, Lee Dae Woo, Yim Ga Won, Nam Eun Ji, Kim Sunghoon, Kim Sang Wun, Kim Young Tae
Institute of Women's Life Medical Science, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Obstetrics and Gynecology, Yonsei University Graduate School, Seoul, Republic of Korea.
Int J Oncol. 2015 Feb;46(2):521-30. doi: 10.3892/ijo.2014.2758. Epub 2014 Nov 17.
The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervical cancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervical cancer. HOTAIR expression was determined in cervical cancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervical cancer cell lines, we used the CCK-8 assay, wound healing migration and matrigel invasion assay. The expression level of HOTAIR in cervical cancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervical cancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervical cancer cell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervical cancer.
许多长链非编码RNA(lncRNA)在人类癌症中的功能仍有待阐明。据报道,lncRNA Hox转录本反义基因间RNA(HOTAIR)可重新编程染色质组织并促进乳腺癌和结直肠癌转移,lncRNA在宫颈癌中的作用刚刚开始被研究。在本研究中,我们检测了HOTAIR在宫颈癌中的表达及其功能作用。通过实时聚合酶链反应测定了111例宫颈癌组织和40例相应正常组织中HOTAIR的表达,并分析了其与临床参数及预后的相关性。为了确定HOTAIR敲低和过表达对宫颈癌细胞系的影响,我们使用了CCK-8检测、伤口愈合迁移和基质胶侵袭检测。宫颈癌组织中HOTAIR的表达水平高于相应的非癌组织。HOTAIR高表达与淋巴结转移及总生存期降低相关。多因素分析表明,HOTAIR是预测宫颈癌复发的一个预后因素。敲低HOTAIR可降低宫颈癌细胞系的细胞增殖、迁移和侵袭。此外,HOTAIR调节血管内皮生长因子、基质金属蛋白酶-9和上皮-间质转化(EMT)相关基因的表达,这些基因对细胞运动和转移很重要。因此,HOTAIR可能通过上调VEGF、MMP-9和EMT相关基因来促进肿瘤侵袭性。这些发现表明,HOTAIR可能是预测复发和预后的一种新型生物标志物,并有望成为宫颈癌的治疗靶点。