Huang Lu, Gan Xiaoqin, He Li, Wang Luying, Yu Jie
Department of Obstetrics and Gynaecology, Chengdu Women and Children's Central Hospital, Chengdu, Sichuan 610031, P.R. China.
Exp Ther Med. 2019 Sep;18(3):2314-2322. doi: 10.3892/etm.2019.7799. Epub 2019 Jul 19.
Long non-coding RNA NCK1-antisense 1 (AS1) has recently been demonstrated to promote cell proliferation and induce cell cycle progression through the crosstalk NCK1-AS1/microRNA (miR)-6857/cyclin dependent kinase 1 pathway in cervical cancer. However, the regulatory mechanism of NCK1-AS1 in cervical cancer growth and metastasis remains largely unclear. In the present study, it was identified that NCK1-AS1 was significantly upregulated in cervical cancer tissues compared with the levels in adjacent non-tumour tissues. High expression levels of NCK1-AS1 were associated with tumour progression and poor prognosis in patients with cervical cancer. Silencing of NCK1-AS1 expression significantly decreased the levels of proliferation and migration of cervical cancer cells, and decreased the protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. The results of the luciferase reporter gene assay indicated that there was an miR-134 binding site within the NCK1-AS1 gene in cervical cancer cells. miR-134 was significantly downregulated in cervical cancer tissues compared with the miR-134 levels in adjacent non-tumour tissues, and the expression level of miR-134 was inversely correlated with the NCK1-AS1 expression levels in cervical cancer tissues. Knockdown of miR-134 attenuated the inhibitory effects of NCK1-AS1 downregulation on the proliferation and migration of cervical cancer cells. Therefore, the data from the present study suggested that NCK1-AS1 serves a promotive role in cervical cancer cell proliferation and migration by functioning as a molecular sponge for miR-134. NCK1-AS1 may become a novel therapeutic target for cervical cancer.
长链非编码RNA NCK1反义链1（AS1）最近被证明可通过宫颈癌中的NCK1-AS1/微小RNA（miR）-6857/细胞周期蛋白依赖性激酶1途径促进细胞增殖并诱导细胞周期进程。然而，NCK1-AS1在宫颈癌生长和转移中的调控机制仍不清楚。在本研究中，发现与相邻非肿瘤组织相比，NCK1-AS1在宫颈癌组织中显著上调。NCK1-AS1的高表达水平与宫颈癌患者的肿瘤进展和不良预后相关。沉默NCK1-AS1表达可显著降低宫颈癌细胞的增殖和迁移水平，并降低基质金属蛋白酶（MMP）-2和MMP-9的蛋白表达水平。荧光素酶报告基因检测结果表明，宫颈癌细胞的NCK1-AS1基因内存在一个miR-134结合位点。与相邻非肿瘤组织中的miR-134水平相比，miR-134在宫颈癌组织中显著下调，且miR-134的表达水平与宫颈癌组织中NCK1-AS1的表达水平呈负相关。敲低miR-134可减弱NCK1-AS1下调对宫颈癌细胞增殖和迁移的抑制作用。因此，本研究数据表明，NCK1-AS1通过作为miR-134的分子海绵在宫颈癌细胞增殖和迁移中发挥促进作用。NCK1-AS1可能成为宫颈癌的一个新的治疗靶点。
