背景:宫颈鳞状细胞癌(CESC)是全球最常见的妇科恶性肿瘤。尽管癌症易感性18(CASC18)基因参与了癌症生物学的调控,其在CESC中的具体作用没有得到很好的表征。
方法:通过生物信息学分析预测CASC18相关轴,并使用定量实时PCR进一步验证了竞争性内源RNA(ceRNA)的相互作用,西方印迹,RNA下拉,和荧光素酶报告基因测定。进行Transwell和伤口愈合测定以验证CASC18对SiHa和HeLa细胞运动性的影响。
结果:我们发现CESC组织中CASC18上调。此外,干扰CASC18减弱NUAK1介导的上皮间质转化(EMT),从而抑制癌细胞运动。此外,通过miR-5586-5p抑制剂转染,CASC18敲低对CESC细胞的影响得到部分挽救.此外,我们的研究结果表明,CASC18作为一种ceRNA,通过形成miR-5586-5p增强NUAK1的表达.
结论:我们的研究显示了一种新型的CASC18/miR-5586-5p/NUAK1ceRNA轴,可以通过调节CESC中的EMT来调节细胞侵袭和迁移。这些发现表明,CASC18可能作为CESC治疗的新治疗靶点。
BACKGROUND: Cervical squamous cell carcinoma (CESC) is the most common gynecological malignancy worldwide. Although the cancer susceptibility 18 (CASC18) gene was involved in the regulation of cancer biology, its specific role in CESC is not well characterized.
METHODS: CASC18-related axis was predicted by bioinformatic analyses, and the competing endogenous RNA (ceRNA) interaction was further validated using quantitative real-time PCR, western blotting, RNA pulldown, and luciferase reporter assays. Transwell and wound healing assays were performed to verify the effect of CASC18 on SiHa and HeLa cell motility.
RESULTS: We found that CASC18 was upregulated in CESC tissues. Moreover, interference with CASC18 attenuated NUAK1-mediated epithelial-mesenchymal transition (EMT) and thus suppressed cancer cell motility. Furthermore, the effects of CASC18 knockdown on CESC cells were partly rescued by transfection with the miR-5586-5p inhibitor. Additionally, our findings indicated that CASC18 acts as a ceRNA to enhance NUAK1 expression by sponging miR-5586-5p.
CONCLUSIONS: Our study showed a novel CASC18/miR-5586-5p/NUAK1 ceRNA axis that could regulate cell invasion and migration by modulating EMT in CESC. These findings suggest that CASC18 may potentially serve as a novel therapeutic target in CESC treatment.