lncRNA DLX6-AS1 Promotes Proliferation of Laryngeal Cancer Cells by Targeting the miR-26a/TRPC3 Pathway

• Main Authors: Liu Y, Liu X, Zhang X, Deng J, Zhang J, Xing H
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-04-01
• Series: Cancer Management and Research
• Subjects: laryngeal cancer; dlx6-as1; mir-26a; mitochondria; trpc3
• Online Access: https://www.dovepress.com/lncrna-dlx6-as1-promotes-proliferation-of-laryngeal-cancer-cells-by-ta-peer-reviewed-article-CMAR

Yan Liu,1 Xinyi Liu,1 Xiaofeng Zhang,2 Jinhu Deng,2 Jian Zhang,2 Hao Xing3 1Department of Otolaryngology & Head & Neck Surgery, Weihai Municipal Hospital of Shandong University, Weihai, Shandong Province 264200, People’s Republic of China; 2Department of Otolaryngology and Head and Neck Surgery, Second Weihai Municipal Hospital Affiliated to Qingdao University, Weihai 264200, Shandong Province, People’s Republic of China; 3Department of Thyroid Surgery, Taian City Central Hospital, Taian 271099, Shandong Province, People’s Republic of ChinaCorrespondence: Hao XingDepartment of Thyroid Surgery, Taian City Central Hospital, No. 29 in Longtan Road, Taian 271099, Shandong Province, People’s Republic of ChinaTel [phone]Email [e-mail]: 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.Keywords: laryngeal cancer, DLX6-AS1, miR-26a, mitochondria, TRPC3