Cmar_a_237181 2685..2695

Yan Liu Xinyi Liu Xiaofeng Zhang Jinhu Deng Jian Zhang Hao Xing 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 China 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: lncRNADLX6-AS1 had increased expression in tumor tissues comparedwith 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 byDLX6-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.