Non-alcoholic fatty liver disease (NAFLD) is a relevant risk factor for developing hepatocellular carcinoma (HCC). Steatohepatitic HCC (SH-HCC), characterized by HCC with steatosis, is influenced by lipid metabolism disorders. A hypoxic microenvironment is common in HCC and affects lipid metabolism. However, whether hypoxia-induced HIF-2α upregulation exacerbates lipid accumulation to contribute to SH-HCC progression remains unclear. In this study, we demonstrated that HIF-2α was elevated in tissues from NAFLD-HCC patients and was associated with survival. Under hypoxic conditions, upregulated HIF-2α was accompanied by lipid accumulation and PI3K-AKT-mTOR pathway activation. HIF-2α knockdown (KD) in steatotic HCC ameliorated triglyceride accumulation and steatosis. HIF-2α-KD steatotic HCC showed minimal lipid synthesis in a hypoxic environment, which contributes to a reduction in malignant behaviours. However, treatment with MHY1485 restored these behaviours. STAM mice, a mouse model that develops NAFLD-HCC, exhibit more rapid tumour progression upon exposure to hypoxia. STAM mice treated with INK-128 presented abrogated mTOR expression and tumour progression under hypoxic conditions with lower triglycerides and steatosis. In conclusion, in a hypoxic microenvironment, HIF-2α upregulation promotes steatotic HCC progression by activating lipid synthesis via the PI3K-AKT-mTOR pathway. Therefore, HIF-2α can be a biomarker and target in developing specific therapeutic measures for NAFLD-HCC patients.

Background miR-429 and TLN1 have been shown to affect the biological behaviours of many carcinomas. However, their effects in nasopharyngeal carcinoma (NPC) are not yet clear. Here, we investigated their regulatory relationships and effects on NPC cells. Methods TargetScan was used to predict the regulatory relationships of miR-429 and TLN1 in NPC cells. Then, Western blotting and quantitative real-time PCR (qPCR) were performed to examine TLN1 levels, and qPCR was used to determine miR-429 levels in NPC cell lines with different metastatic characteristics (5-8F, CNE-2, CNE-1, 6-10B and NP69), to investigate whether TLN1 and miR-429 are correlated with the metastatic characteristics of these cells. Next, we upregulated or downregulated miR-429 in 5-8F and 6-10B cells, which have different tumourigenicity and transferability, and examined TLN1 expression by western blotting and qPCR after transfection. QPCR was also performed to confirm successful transfection of miR-429 mimic into 5-8F and 6-10B cells. Dual luciferase reporter gene assay was performed to investigate whether miR-429 regulates TLN1 by binding to its 3′UTR. After transfection, Cell Counting Kit-8 (CCK8) and IncuCyte were used to examine the proliferation of these cells, and wound-healing assay, Transwell migration assay, and invasion assays were performed to investigate the changes in migration and invasion after transfection. Results Western blotting and qPCR analyses showed that the protein level of TLN1 was negatively correlated with miR-429 in NPC cell lines ( P < 0.05), while the mRNA level showed no relation with miR429 expression ( P > 0.05). In addition, cells with high transferability showed high TLN1 expression at the protein level, while miR429 expression showed the opposite trend ( P < 0.05), but there were no differences at the mRNA level between the different cell lines. Overexpression of miR429 in 5-8F and 6-10B cells was accompanied by downregulation of TLN1 at the protein level ( P < 0.05), while there were no significant differences at the mRNA level ( P > 0.05). In addition, transferability, proliferation, and invasion were downregulated by miR429 overexpression ( P < 0.05). However, dual-luciferase reporter gene assay indicated that TLN1 was not a direct target of miR-429. Conclusion This study showed that miR-429 functions as a tumour suppressor in NPC by downregulation of TLN1, although the relationship is not direct.

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Background: Acquired resistance is a challenge for epidermal growth factor receptor (EGFR) mutant nonsmall cell lung cancer. Here, we propose a novel treatment strategy based on recent lipid metabolism work. Methods:We applied a variety of experimental methods such as immunoblotting, MTT, si-RNA, and animal models, to demonstrate the relationship between EGFR and low-density lipoprotein receptor (LDLR) and the effects of statin monotherapy, and TKI monotherapy, and their combination on cell proliferation at the cell level and animal level.Results: LDLR has a positive correlation with EGFR, EGFR signaling upregulates LDLR expression through the SREBP-1 dependent pathway, EGFR mutation cells count on lipids to survive and grow.Combined with a molecule-targeted drug, atorvastatin not only enhances the treatment effect in vitro, but also mitigates the growth of NSCLC in vivo. In this animal experiment, the combination medicine (atorvastatin with TKI) has a better tumor suppression effect on NSCLC. In HCC827 cell line, the average tumor shrinkage is about 68% in Gefitinib group, and about 49% in atorvastatin group, but about 89% in combination group. In H1975 cell line, the average tumor shrinkage is about 18% in Osimertinib group, and about 8% in atorvastatin group, but about 44% in combination group.Conclusions: the combination of an EGFR-TKI and a statin for EGFR mutant NSCLC may be a novel tumor inhibiting treatment.

Little is known about the clinical significance of CD47 expression and its association with Epstein-Barr virus (EBV) infection in patients with nasopharyngeal carcinoma (NPC). The aim of this study was to clarify the prognostic value and role of CD47 in EBV-associated NPC. Materials and Methods: Sixty-six cases of non-metastatic NPC were retrospectively reviewed. Tissues were collected for immunohistochemical staining of CD47 and the EBVencoded oncoprotein latent membrane protein 1 (LMP1). Western blotting and quantitative real-time PCR were performed to determine the CD47 and LMP1 levels in common human NPC cell lines. Additionally, CD47 and LMP1 expression in a constructed EBV-positive human NPC cell (CNE-2-EBV+) and a stable cell line transfected with LMP1 plasmid (CNE-2-LMP1) was assessed. Next, we used Western blotting to assess the decrease in CD47 expression on CNE-2-LMP1 cells after transfecting them with small interfering RNA (siRNA)-targeting LMP1. Results: In NPC patients, CD47 overexpression was significantly associated with disease recurrence (P=0.010), leading to poorer disease-free survival (DFS; P=0.002) and overall survival (P=0.021). Multivariate Cox proportional hazards models demonstrated that CD47 (HR=5.452, P=0.016) was an independent prognostic factor of DFS. Moreover, CD47 expression was associated with plasma EBV-DNA copy number and LMP1 tissue expression. Among the human NPC cell lines, CD47 and LMP1 expression was notably higher in the EBV-positive C666-1 cell line than in the EBV-negative cell lines. Furthermore, EBV infection upregulated CD47 expression via LMP1-mediated pathways in human NPC cells. Conclusion: This study indicated that CD47 is related to EBV infection in NPC patients, and it is a feasible biomarker.