Department of Gynaecology, The Frist People's Hospital of Zhangjiagang Affiliated to Suzhou University, Zhangjiagang, China.
Bioengineered. 2022 Feb;13(2):2567-2584. doi: 10.1080/21655979.2021.2018975.
As the fourth commonest malignancy among females worldwide, cervical cancer (CC) poses a huge challenge to human health. The pivotal regulatory roles of lncRNAs in cancers have been highlighted. LOXL1 antisense RNA 1 (LOXL1-AS1) has been reported to play a key role in cervical squamous cell carcinoma and other various cancers. Thus, we investigated the roles and mechanisms of lncRNA LOXL1-AS1 in CC. The experiments demonstrated that LOXL1-AS1 downregulation inhibited tumor growth and metastasis and proliferation of CC cells. The results of RT-qPCR demonstrated that LOXL1-AS1 and ectodermal-neural cortex 1 (ENC1) expression levels were upregulated in CC cells and tissues, while microRNA-423-5p (miR-423-5p) level was downregulated. As subcellular fractionation assays, RNA pull down assays and luciferase reporter assays revealed, LOXL1-AS1 bound to miR-423-5p and miR-423-5p targeted ENC1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, wound healing and colony formation assays demonstrated that miR-423-5p upregulation and LOXL1-AS1 downregulation inhibited CC cell proliferation and migration, while ENC1 upregulation attenuated the inhibitory effects of miR-423-5p upregulation on the malignant phenotypes of CC cells. Western blotting was conducted to measure protein levels and the results showed that ENC1 knockdown inhibited the activation of ERK/MEK pathway. In summary, the LOXL1-AS1/miR-423-5p/ENC1 axis accelerates CC development through the MEK/ERK pathway.
作为全球女性中第四大常见的恶性肿瘤,宫颈癌(CC)对人类健康构成了巨大挑战。lncRNAs 在癌症中的关键调节作用已得到强调。已经报道 LOXL1 反义 RNA 1(LOXL1-AS1)在宫颈鳞状细胞癌和其他各种癌症中发挥关键作用。因此,我们研究了 lncRNA LOXL1-AS1 在 CC 中的作用和机制。实验表明,下调 LOXL1-AS1 抑制了 CC 细胞的肿瘤生长和转移以及增殖。RT-qPCR 的结果表明,LOXL1-AS1 和外胚层-神经皮质 1(ENC1)在 CC 细胞和组织中的表达水平上调,而 microRNA-423-5p(miR-423-5p)水平下调。作为亚细胞分级测定、RNA 下拉测定和荧光素酶报告测定的结果,LOXL1-AS1 与 miR-423-5p 结合,miR-423-5p 靶向 ENC1。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定、划痕愈合和集落形成测定表明,上调 miR-423-5p 和下调 LOXL1-AS1 抑制 CC 细胞增殖和迁移,而上调 ENC1 减弱了上调 miR-423-5p 对 CC 细胞恶性表型的抑制作用。进行了 Western blot 以测量蛋白质水平,结果表明 ENC1 敲低抑制了 ERK/MEK 通路的激活。总之,LOXL1-AS1/miR-423-5p/ENC1 轴通过 MEK/ERK 通路加速了 CC 的发展。