AbstractObjective To analyze the association between the expression of ubiquinone oxidoreductase complex assembly factor 4 (NDUFAF4) and clinical prognosis of patients with hepatocellular carcinoma (HCC), evaluate the effect of NDUFAF4 on the radiosensitivity of human HCC cell lines, and unravel the underlying mechanism. Methods The online database and HCC tissue samples were used to investigate the expression of NDUFAF4, and the correlation between NDUFAF4 expression level and clinical prognosis. The si-NDUFAF4 plasmid which down-regulated the expression level of NDUFAF4 was transferred into HepG2 and Huh7 cells. The radiosensitivity of HCC cell lines was detected by clone formation experiment. Nude mice were prepared for tumor-bearing experiment. The β-catenin level was detected by immunofluorescent staining. The expression levels of E-cadherin and N-cadherin proteins were determined by Western blot. Results Bioinformatics results confirmed that NDUFAF4 was significantly up-regulated in HCC tissues, and the higher the expression level, the worse the patients' clinical prognosis (P<0.05). The expression level of NDUFAF4 in HCC tissues was significantly higher than that in the adjacent tissues. Clone formation experiment confirmed that knockdown of NDUFAF4 significantly decreased the survival rate of HCC cells (P<0.01). In vivo experiment showed that knockdown of NDUFAF4 could prevent the proliferation of HCC cells and down-regualte the expression levels of β-catenin and Ki-67. Knockdown of NDUFAF4 significantly down-regulated the expression level of β-catenin protein in the nucleus of HCC cell lines, suggesting that NDUFAF4 could activate the WNT/β-catenin signaling pathway. Knockdown of NDUFAF4 significantly up-regulated the expression level of E-cadherin and down-regulated that of N-cadherin. Conclusions Knockdown of NDUFAF4 can significantly enhance the radiosensitivity of HCC cell lines by inhibiting the WNT/β-catenin signaling pathway. The expression level of NDUFAF4 is intimately correlated with clinical prognosis. NDUFAF4 can be considered as a new target for lowering the radiation resistance of HCC.
You Jie,Wang Xiumin,Meng min et al. Mechanism of the role of NDUFAF4 in increasing radiation resistance of hepatocellular carcinoma by activating Wnt/β-catenin signaling pathway[J]. Chinese Journal of Radiation Oncology, 2022, 31(7): 643-648.
You Jie,Wang Xiumin,Meng min et al. Mechanism of the role of NDUFAF4 in increasing radiation resistance of hepatocellular carcinoma by activating Wnt/β-catenin signaling pathway[J]. Chinese Journal of Radiation Oncology, 2022, 31(7): 643-648.
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