Wan Hongyu, Tian Yi, Zhao Juan, Su Xiao
Department of Gastroenterrology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201100, China.
J Oncol. 2021 Nov 10;2021:9046798. doi: 10.1155/2021/9046798. eCollection 2021.
Inhibition of aerobic glycolysis is a hopeful method for cancer treatment. In this study, we aimed to explore LINC00665/miR-214-3p/MAPK1 role in regulating cell viability and aerobic glycolysis in hepatocellular carcinoma (HCC). The expressions of LINC00665 in 50 paired HCC tissues and normal tissues were determined by qRT-PCR. Pearson analysis was applied to evaluate the association between the expression levels of miR-214-3p, LINC00665, and MAPK1 in HCC tissues. The interactions between miR-214-3p and LINC00665 or MAPK1 were determined by luciferase reporter assay and RNA immunoprecipitation. CCK-8 and colony formation assays were used for cell viability evaluation. Lactate production, glucose consumption, and ATP levels were measured to assess Warburg effect. The results showed that LINC00665 was overexpressed in HCC, which positively associated with MAPK1 level and negatively associated with miR-214-3p level in HCC tissues. Overexpression of LINC00665 led to significant enhancements in cell viability and colony formation, whereas this effect was weakened when miR-214-3p was overexpressed or MAPK1 was downregulated. In addition, deletion of LINC00665 expression repressed tumor formation . Mechanically, LINC00665 increased MAPK1 expression through binding to miR-214-3p. Collectively, this study revealed that LINC00665 accelerated cell growth and Warburg effect through sponging miR-214-3p to increase MAPK1 expression in HCC.
抑制有氧糖酵解是一种有前景的癌症治疗方法。在本研究中，我们旨在探讨LINC00665/miR-214-3p/MAPK1在调节肝细胞癌（HCC）细胞活力和有氧糖酵解中的作用。通过qRT-PCR测定50对HCC组织和正常组织中LINC00665的表达。采用Pearson分析评估HCC组织中miR-214-3p、LINC00665和MAPK1表达水平之间的相关性。通过荧光素酶报告基因测定和RNA免疫沉淀确定miR-214-3p与LINC00665或MAPK1之间的相互作用。使用CCK-8和集落形成试验评估细胞活力。测量乳酸产生、葡萄糖消耗和ATP水平以评估Warburg效应。结果显示，LINC00665在HCC中过表达，在HCC组织中与MAPK1水平呈正相关，与miR-214-3p水平呈负相关。LINC00665的过表达导致细胞活力和集落形成显著增强，而当miR-214-3p过表达或MAPK1下调时，这种效应减弱。此外，LINC00665表达缺失抑制肿瘤形成。机制上，LINC00665通过与miR-214-3p结合增加MAPK1表达。总体而言，本研究揭示LINC00665通过海绵化miR-214-3p增加HCC中MAPK1表达，从而加速细胞生长和Warburg效应。
