The NRF2-dependent transcriptional axis, XRCC5/hTERT drives tumor progression and 5-Fu insensitivity in hepatocellular carcinoma.

ABSTRACT: Human telomerase reverse transcriptase (hTERT) is highly expressed in many tumors and is essential for tumorigenesis and metastasis in multiple cancers. However, the molecular mechanisms underlying its high expression level in hepatocellular carcinoma (HCC) remain unclear. In this study, we identified X-ray repair cross-complementing 5 (XRCC5), a novel hTERT promoter-binding protein in HCC cells, using biotin-streptavidin-agarose pull-down assay. We found that XRCC5 was highly expressed in HCC cells, in which it transcriptionally upregulated hTERT. Functionally, the transgenic expression of XRCC5 promoted HCC progression and 5-fluorouracil resistance, whereas short hairpin RNA knockdown of XRCC5 had converse effects in vitro and in vivo. Moreover, hTERT overexpression reverse

SUBMITTER: Liu T 

PROVIDER: S-EPMC8762376 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature