Abstract：Abstract: Many members of the Thanatos-associated proteins (THAP) family have been proved to be closely related to cell proliferation, apoptosis and cancer, but the function of THAP8 is still unclear. In order to in-vestigate the expression of THAP8 in cancer, the TCGA and Oncomine databases were analyzed and it was found that the expression of THAP8 mRNA in lung cancer tissues was significantly higher than that in nor-mal tissues adjacent to lung cancer. Real-time quantitative PCR was then performed to analyze differential expressions of THAP8 in 22 pairs of lung cancer and adjacent non-cancerous tissues, and the result was consistent with that of database analysis. To explore the reason for THAP8 overexpression in cancer tissues, JASPAR software was used to predict the transcription factor binding sites within the THAP8 promoter, and four hypoxia response elements (HREs) were identified. The luciferase reporter assay demonstrated that the hypoxia-inducible factor-1α (HIF-1α) can bind to the HREs and promote the transcription of the THAP8 gene. In the CoCl2-induced hypoxia model, with increasing CoCl2 concentration, expression levels of HIF-1α and THAP8 proteins increased. Overexpression of HIF-1α in Beas-2B cells promoted THAP8 expression. In order to study the role of THAP8 in lung cancer cells, lentivirus-mediated shRNA was used to inhibit the expression THAP8 gene, and the effects of THAP8 knockdown on the biological behavior of lung cancer cells were analyzed. The results showed that knockdown of THAP8 gene in both H460 and H1437 cells sig-nificantly decreased cell viability, colony formation and invasion. These results indicate that THAP8 can be induced by hypoxia, promoting the viability, colony formation and invasion of lung cancer cells, and proves a novel oncogene.
引用本文:
刘顺莲, 宁贻崇, 刘凯丽, 陈思文, 周 琳, 李美玲, 张 晴, 周建林. THAP8基因可被HIF-1ɑ上调并促进肺癌细胞活力、克隆形成和侵袭[J]. 生命科学研究, 2021, 25(3): 217-224.
LIU Shun-lian, NING Yi-chong, LIU Kai-li, CHEN Si-wen, ZHOU Lin, LI Mei-ling, ZHANG Qing, ZHOU Jian-lin. THAP8 is Upregulated by HIF-1α and Promotes Viability, Colony Formation and Invasion of Lung Cancer Cells. Life Science Research, 2021, 25(3): 217-224.
