Xu Haiting, Liu Huazhen, Li Zi, Xu Qin, Lin Nan, Li Xiaoyang
Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China.
Department of Burn, Changhai Hospital Affiliated Naval Medical University, Shanghai, 200433, People's Republic of China.
Clin Cosmet Investig Dermatol. 2022 Jun 17;15:1109-1117. doi: 10.2147/CCID.S370969. eCollection 2022.
Cutaneous melanoma (CM) accounts for about 90% of all melanoma cases. HIF-1α overexpression is associated with poor prognosis in many cancers including CM. Hence, we characterized differentially expressed genes (DEGs) in the response of CM cells to normoxia and hypoxia.
We first successfully constructed cell hypoxia model and then performed RNA-seq to explore the changes of gene transcription in CM cells during hypoxia. The highest expression of the six genes was detected using qRT-PCR and Western blot assays. The binding sites between BIRC7 promoter and HIF-1α was explored by luciferase assay. Cellular function assays were used to observe the role of BIRC7 in the effect of hypoxia on tumor progression.
Compared with the transcriptome data of the control group, a total of 2601 DEGs were identified in the hypoxic group. There were 1517 genes with significantly higher expression and 1084 genes with lower expression in the hypoxic group. Among them, OSCAR, BIRC7, HBA1, SFN, GOLT1A, and BEX2 were significantly up-regulated in the hypoxic group. BIRC7 expression was most significantly up-regulated and a downstream factor of HIF-1α. We highlighted that knockdown of BIRC7 reversed the positive effects of HIF-1α on A875 and M14 cells.
Our findings demonstrated that BIRC7 was a downstream factor of HIF-1α and reversed the effect of hypoxia on promoting tumor progression of CM cells.
皮肤黑色素瘤（CM）约占所有黑色素瘤病例的90%。缺氧诱导因子-1α（HIF-1α）过表达与包括CM在内的许多癌症的不良预后相关。因此，我们对CM细胞在常氧和缺氧反应中的差异表达基因（DEG）进行了表征。
我们首先成功构建了细胞缺氧模型，然后进行RNA测序以探索CM细胞在缺氧过程中基因转录的变化。使用qRT-PCR和蛋白质免疫印迹分析检测六个基因的最高表达。通过荧光素酶测定法探索BIRC7启动子与HIF-1α之间的结合位点。使用细胞功能测定法观察BIRC7在缺氧对肿瘤进展影响中的作用。
与对照组的转录组数据相比，缺氧组共鉴定出2601个DEG。缺氧组中有1517个基因表达显著升高，1084个基因表达降低。其中，OSCAR、BIRC7、HBA1、SFN、GOLT1A和BEX2在缺氧组中显著上调。BIRC7表达上调最为显著，是HIF-1α的下游因子。我们强调，敲低BIRC7可逆转HIF-1α对A875和M14细胞的积极作用。
我们的研究结果表明，BIRC7是HIF-1α的下游因子，可逆转缺氧对CM细胞肿瘤进展的促进作用。
