Abstract
Abnormal expression of human telomerase reverse transcriptase (hTERT) has been widely identified in tumors, but the relevant mechanism is not well known. This study aims to investigate the role and mechanism of hTERT in gastric cancer metastasis. Gastric cancer and adjacent non-tumor tissues were collected and the expression levels of hTERT and Gli1 were detected by immunohistochemistry. The results demonstrated that hTERT and Gli1 expression levels in gastric cancer tissue were significantly higher than adjacent non-tumor tissues. Western blot and quantitative real-time PCR were used to an identified expression of the related protein in BGC-823 and SGC-7901 cells. The interactions between hTERT and Sp1 were tested by co-immunoprecipitation experiments. Chromatin immunoprecipitation was performed to confirm that Sp1 and hTERT could bind to the Gli1 promoter. Chromatin reimmunoprecipitation assay further demonstrated that both hTERT and Sp1 bind to the Sp1 site of the Gli1 promoter. Moreover, the hTERT, Sp1, and Gli1 were upregulate was verified in human gastric cancer tissues. These results showed that the expression levels of hTERT in GC tissues were strongly closed to the depth of invasion, lymph node metastasis, TNM (tumor, node, metastasis) stage, and distant metastasis. By combining Sp1 and Gli1 promoter, hTERT upregulated Gli1 expression and promoted invasion and metastasis of GC cells. Overall, these data provide a new molecular mechanism of hTERT to promotes gastric cancer progression. Targeting the hTERT/Sp1/Gli1 axis may represent a new therapeutic strategy.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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This work was supported by National Natural Science Foundation of China (No. 81502554).
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DZ and EL conceived of the study; LW and EL designed the experiments; LW, SW, DZ, BT, LT performed the experiments; YL, YL, and MY performed analysis and interpretation of data; LW and EL wrote the manuscript; GY and DZ critically reviewed the manuscript. all authors have read and approved the manuscript.
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Wu, L., Wang, S., Tang, B. et al. Human telomerase reverse transcriptase (hTERT) synergistic with Sp1 upregulate Gli1 expression and increase gastric cancer invasion and metastasis. J Mol Histol 52, 1165–1175 (2021). https://doi.org/10.1007/s10735-021-10019-9
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DOI: https://doi.org/10.1007/s10735-021-10019-9