Nuclear factor E2-related factor 2 (Nrf2 or NFE2L2) is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance. Our early observations also found that expression of Nrf2 was up-regulated in kinds of cancer including human hepatocellular carcinoma (HCC) cells. But there are limited reports about the expression, significance, function of Nrf2 in HCC. First, Nrf2 expression was analyzed in HCC cell lines and tumor samples. Then, the relationship of Nrf2 with clinicopathological factors and survival were analyzed. Further, the effect of Nrf2 on cell proliferation, apoptosis, and metastasis was examined in vitro by modulating expression of Nrf2 through specific shRNA or expression plasmid. Last, the potential mechanisms were also investigated. Nrf2 was up-regulated in HCC, and expression of Nrf2 was correlated with tumor differentiation, metastasis, and tumor size. Univariate and multivariate analyses indicated that high Nrf2 expression might be a poor prognostic factor. Further studies demonstrated that inhibition of Nrf2 expression inhibited proliferation by inducing apoptosis and repressed invasion, and up-regulation of Nrf2 expression resulted in opposite phenotypes. Moreover, there are positive correlation between Nrf2 expression and that of Bcl-xL and MMP-9. Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma partly through regulating expression of Bcl-xL and MMP-9.

Propofol is one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, but the effect of propofol on gallbladder cancer is not clear. NF-E2-related factor 2 (Nrf2) is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance. The aims of the current study were to evaluate effects of propofol on the behavior of human GC cells and role of Nrf2 in these effects.

Cancer patients with different stages can benefit from radiotherapy, but there are still limited due to inherent or acquired radioresistance. The epithelial-mesenchymal transition (EMT) is a complex biological process that is implicated in malignant characteristics of cancer, such as radioresistance. Although the possible mechanisms of EMT-dependent radioresistance are being extensively studied, there is a lack of a clear picture of the overall signaling of EMT-mediated radioresistance. In this review, we highlight the role and possible molecular mechanisms of EMT in cancer radioresistance, in particular to EMT-associated signaling pathway, EMT-inducing transcription factors (EMT-TFs), EMT-related non-coding RNAs. The knowledge of EMT-associated mechanisms of radioresistance will offer more potent therapy targets to improve the radiotherapy responses.

Oxaliplatin resistance undermines its curative effects on cancer and usually leads to local recurrence. The oxidative stress induced DNA damage repair response is an important mechanism for inducing oxaliplatin resistance by activating autophagy. ELISA is used to detect target genes expression. TMT-based quantitative proteomic analysis was used to investigate the potential mechanisms involved in NORAD interactions based on GO analysis. Transwell assays and apoptosis flow cytometry were used for biological function analysis. CCK-8 was used to calculate IC50 and resistance index (RI) values. Dual-luciferase reporter gene assay, RIP and ChIP assays, and RNA pull-down were used to detect the interaction. Autophagy flux was evaluated using electron microscope and western blotting. Oxidative stress was enhanced by oxaliplatin; and oxaliplatin resistance gastric cancer cell showed lower oxidative stress. TMT labeling showed that NORAD may regulate autophagy flux. NORAD was highly expressed in oxaliplatin-resistant tissues. In vitro experiments indicate that NORAD knockdown decreases the RI (Resistance Index). Oxaliplatin induces oxidative stress and upregulates the expression of NORAD. SGC-7901 shows enhanced oxidative stress than oxaliplatin-resistant cells (SGC-7901-R). NORAD, activated by H3K27ac and CREBBP, enhanced the autophagy flux in SGC-7901-R to suppress the oxidative stress. NORAD binds to miR-433-3p and thereby stabilize the ATG5- ATG12 complex. Our findings illustrate that NORAD, activated by the oxidative stress, can positively regulate ATG5 and ATG12 and enhance the autophagy flux by sponging miR-433-3p. NORAD may be a potential biomarker for predicting oxaliplatin resistance and mediating oxidative stress, and provides therapeutic targets for reversing oxaliplatin resistance.