lncRNA DLX6-AS1 Promotes Proliferation of Laryngeal Cancer Cells by Targeting the miR-26a/TRPC3 Pathway
lncRNA DLX6-AS1 Promotes Proliferation of Laryngeal Cancer Cells by Targeting the miR-26a/TRPC3 Pathway
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DOI：
10.2147/cmar.s237181
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Xing, Hao
中科院分区：
文献类型：
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作者：
Liu, Yan;Liu, Xinyi;Xing, Hao
目的：喉癌是头颈癌中最常见的肿瘤类型。早期诊断被认为是改善预后的重要策略。 lncRNA DLX6-AS1已被证明可以调节多种类型癌症的肿瘤表型，但DLX6-AS1在喉癌中的作用及其具体机制尚不清楚。 方法：采用喉癌患者的组织样本和相应的临床数据进行详细分析。研究了喉癌细胞系 HEp-2 和 Tu-177。评估了细胞增殖、ROS 产生、线粒体呼吸功能、细胞内和线粒体钙流入。使用蛋白质印迹、定量 RT-PCR 和荧光素酶测定来分析相互作用。建立异种移植肿瘤模型，分析DLX6-AS1对体内肿瘤生长的影响。结果：与癌旁正常组织相比，lncRNA DLX6-AS1在肿瘤组织中表达增加，临床分期较高的表达量较低分期表达增加，与不良预后相关。详细而言，DLX6-AS1 敲低可降低 HEp-2 和 Tu-177 细胞的细胞增殖并影响关键的线粒体代谢参数。此外，DLX6-AS1 敲低抑制了 TRPC3 介导的线粒体钙摄取和 ROS 产生。此外，miR-26a 充当这两个分子之间的纽带，因为它可以被 DLX6-AS1 吸收，从而调节 TRPC3 的水平。最后，DLX6-AS1/miR-26a/TRPC3 轴在体外和体内均可调节喉癌的增殖。结论：这项研究提供了新的证据，表明一种新型 lncRNA DLX6-AS1 通过调节喉癌中的 miR-26a/TRPC3 轴来调节线粒体钙稳态、呼吸和肿瘤增殖。
Purpose: Laryngeal cancer is the most prevalent tumor type in head and neck cancers. Early diagnosis is considered as an important strategy for improving prognosis. The lncRNA DLX6-AS1 has been shown to modulate tumor phenotypes in several types of cancer, but the role of DLX6-AS1 in laryngeal cancer and its concrete mechanisms are not clear.Methods: Tissue samples from laryngeal cancer patients and corresponding clinical data were used for detailed analysis. The laryngeal cancer cell lines HEp-2 and Tu-177 were studied. Cell proliferation, ROS production, mitochondrial respiratory function, intracellular and mitochondrial calcium influx were assessed. Western blotting, quantitative RT-PCR and luciferase assays were used to analyze the interactions. A xenografted tumor model was established to analyze the effects of DLX6-AS1 on tumor growth in vivo.Results: lncRNA DLX6-AS1 had increased expression in tumor tissues compared with adjacent normal tissues and in higher clinical stages compared with lower stages, which was associated with poor prognosis. In detail, DLX6-AS1 knockdown decreased cell proliferation and affected key mitochondrial metabolic parameters in both HEp-2 and Tu-177 cells. Moreover, DLX6-AS1 knockdown suppressed TRPC3-mediated mitochondrial calcium uptake and ROS production. Furthermore, miR-26a functioned as a link between these two molecules, as it could be absorbed by DLX6-AS1 and thus regulated the levels of TRPC3. Finally, the DLX6-AS1/miR-26a/TRPC3 axis modulated laryngeal cancer proliferation both in vitro and in vivo.Conclusion: This study provides new evidence that a novel lncRNA, DLX6-AS1, regulates mitochondrial calcium homeostasis, respiration and tumor proliferation via modulating the miR-26a/TRPC3 axis in laryngeal cancer.