机构：[1]Department of Head and Neck Surgery, Sichuan Cancer Hospital, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China外科中心头颈外科中心四川省人民医院四川省肿瘤医院头颈外科[2]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China[3]Department of Radiation Oncology, Sichuan Cancer Hospital, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院四川省肿瘤医院
A hypoxic microenvironment plays important roles in the progression of solid tumors, including oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. However, it is not clear whether lncRNAs can regulate hypoxia adaptation of OSCC or which lncRNAs participate in this process. Using a lncRNA microarray, we analyzed the aberrant lncRNA expression profiles in OSCC tissues compared with paired normal oral mucosa and in hypoxic OSCC cells compared with normoxic OSCC cells. The top 10 lncRNAs that had more than threefold increase with P-value <0.01 in both microarray data were validated by qRT-PCR. Among the top 10 lncRNAs, hyaluronan synthase 2 antisense 1 (HAS2-AS1) was the only one that has a hypoxia-responsive element (HRE) on its promoter region and has been validated to increase in OSCC tissues and in cells cultured under hypoxia. Tumor HAS2-AS1 levels were closely associated with lymph node metastasis and hypoxic tumor status in patients with OSCC. Moreover, the hypoxia-induced HAS2-AS1 expression is dependent on HIF-1 which directly binds to and activates the transcription of HAS2-AS1. In addition, HAS2-AS1 mediates hypoxia-induced epithelial mesenchymal transition of OSCC cells via stabilizing HAS2. In conclusion, our results suggest that hypoxia would induce an overexpression of HAS2-AS1 in an HIF-1 dependent manner. The increase of HAS2-AS1 plays important roles mediating the hypoxia-regulated EMT and invasiveness of OSCC.
基金：
Department of Science and Technology of Sichuan Province [2015SZ0053, 2017JQ0040]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81200771, 81302375, 81672690]
第一作者机构：[1]Department of Head and Neck Surgery, Sichuan Cancer Hospital, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
通讯作者：
通讯机构：[1]Department of Head and Neck Surgery, Sichuan Cancer Hospital, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China[3]Department of Radiation Oncology, Sichuan Cancer Hospital, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China[*1]Department of Head and Neck Surgery, Sichuan Cancer Hospital, University of Electronic Science and Technology of China, No. 55, Section 4, Renmin South Road, Chengdu, Sichuan 610041, China.[*2]Department of Radiation Oncology, Sichuan Cancer Hospital, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55, Section 4, Renmin South Road, Chengdu, Sichuan 610041, China.
