Long non-coding RNA00607 as a tumor suppressor by modulating NF-kappaB p65/p53 signaling axis in hepatocellular carcinoma
Menée in vitro et in vivo sur des modèles de carcinome hépatocellulaire, cette étude met en évidence des mécanismes par lesquels, en inhibant la transcription du gène p65, le long ARN non codant RNA00607 exerce une fonction de suppresseur de tumeurs
Accumulating evidence suggests that long-noncoding RNA (lncRNA) play important roles in some malignant tumors. However, the mechanism underlying how lncRNA regulate hepatocellular carcinoma (HCC) process remains largely unknown. In this study, we explored the potential role of LNCRNA 00607 as a novel tumor suppressor in HCC. In the present study, we examined the regulation of LNCRNA 00607 by the important inflammatory cytokine TNF-α and IL-6. We also determined the expression of LINC000607 in 159 HCC tumors and paired adjacent tissues. Effects of LINC000607 in HCC proliferation and apoptosis were examined in vitro in HCC cell lines and invivo tumor xenografts. Furthermore, we also examine underlying mechanism by which LNCRNA 00607 regulates NF-kB p65 and how LIN00607 exerts its tumor suppressor role in HCC. We found that LNCRNA 00607 expression level is lower in HCC tumors compared to matched normal liver tissue, and its low expression predicts worse prognosis in HCC. Functionally, LNCRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity. Mechanistically, LNCRNA 00607 inhibits the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC. Taken together, the findings of this study show that the TNF-α/IL-6-LNCRNA 00607-NF-κB p65/p53 signaling axis represents a novel therapeutic avenue in cancer chemotherapy.
https://academic.oup.com/carcin/advance-article-abstract/doi/10.1093/carcin/bgy113/5086074