Hepatocellular carcinoma (HCC) is considered as a disease of dysfunction of the stem cells. Studies on stem cells have demonstrated that Oct4 plays a pivotal role in embryo regulation. In order to understand the role of Oct4 in HCC and the relationship among Oct4 and wnt/β-catenin and TGF-β signal pathways, we have detected the expression of Oct4, Nanog, Sox2, STAT3 as well as the genes in wnt/β-catenin, and TGF-β families in HCC cell lines and in tumor specimens from HCC patients. The authors found that Oct4 was expressed in all of the four HCC cell lines and the tumor specimens from HCC patients. Some other genes were also expressed in them with different level including Nanog, Sox2, STAT3 and TCF3, wnt10b, β-catenin, ELF, Smad3 and Smad4. The ability of the clone formation and migration of the HepG2 decreased after Oct4 was knockdowned. Silencing of Oct4 and TCF3 in HCC cell line HepG2 revealed that there were complicated relationships among Oct4, wnt/β-catenin family and TGF-β family genes. Knockdowning Oct4 reduced the expression of TGF-β family genes ELF, Smad3, Smad4 and wnt/β-catenin family genes, wnt10b, and β-catenin but increased TCF3. In reverse, knockdowning TCF3 led to the increased expression of Oct4 and TGF-β family genes. In conclusion, the expression of Oct4 in HCC may play an important role as in stem cell. Because Oct4 improves not only the function of wnt/β-catenin, but also the TGF-β signal pathways, the significance of its expression in HCC might be more complicated than we evinced before.

Circular RNA‐synaptosome associated protein 47 (circ‐SNAP47; Hsa_circ_0016760) is oncogenic in non‐small‐cell lung cancer (NSCLC); however, its role is undescribed in cis‐diamminedichloroplatinum II (DDP) resistance. We attempted to investigate its expression, role and mechanism in DDP‐tolerant NSCLC. As a result, circ‐SNAP47 expression was upregulated in human DDP‐tolerant NSCLC tissues and cells, accompanied with WEE1 G2 checkpoint kinase (WEE1) upregulation and microRNA (miR)‐625‐5p downregulation. Functionally, interfering circ‐SNAP47 and/or restoring miR‐625‐5p curbed the 50% inhibitory concentration of DDP, colony formation, cell proliferation and invasion, accompanied with apoptotic rate promotion and depressions of multidrug resistance (MDR) markers MDR1 and MRP1, anti‐apoptosis protein Bcl‐2, and pro‐invasion protein MMP9. Notably, circ‐SNAP47 interference suppressed xenograft tumor growth of DDP‐tolerant NSCLC cells by elevating miR‐625‐5p and descending WEE1. Mechanistically, circ‐SNAP47 directly targeted miR‐625‐5p, and miR‐625‐5p further targeted WEE1. Therefore, circ‐SNAP47‐miR‐625‐5p‐WEE1 axis might participate in chemoresistance and progression of DDP‐tolerant NSCLC.

Background: Previous studies suggested long noncoding RNA metastasis associated with lung adenocarcinoma transcript 1 (lncRNA MALAT1) acted as a tumor promoter to promote cell carcinogenesis in non-small cell lung cancer (NSCLC). MALAT1 was found to exist in serum exosomes of several cancers. However, the role of exosomal-derived MALAT1 in NSCLC remains poorly understood. Materials and Methods: Exosomes were isolated using the ExoQuick precipitation kit. Western blot was used to detect the protein expression of CD3, CD63, apoptosis-and metastasisrelated protein. The expression of MALAT1, microRNA (miR)-515-5p and eukaryotic elongation factor 2 (EEF2) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability, apoptosis, or invasion were measured using 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay, flow cytometry or transwell assay, respectively. The interaction between miR-515-5p and MALAT1 or EEF2 was confirmed by dual-luciferase reporter assay. In vivo experiments were conducted through the murine xenograft model. Results: MALAT1 was highly expressed in serum and cell exosomes from NSCLC patients. MALAT1 knockdown repressed cell proliferation, invasion and induced cell apoptosis in vitro as well as inhibited tumor growth in vivo in NSCLC. Subsequently, we confirmed that MALAT1 was a sponge of miR-515-5p, and EEF2 was a target of miR-515-5p. Furthermore, MALAT1 served as a sponge of miR-515-5p to regulate EEF2 expression in NSCLC cells. More importantly, MALAT1 deletion performed anti-tumor effects by interacting with miR-515-5p/EEF2 axis in vitro and in vivo in NSCLC. Conclusion: MALAT1 knockdown repressed NSCLC tumorigenicity by inhibiting cell proliferation, invasion and promoting apoptosis through regulating miR-515-5p/EEF2, besides, MALAT1 was highly enriched in exosomes of NSCLC, suggesting a possible molecular-targeted therapy for NSCLC patients.

AimTo explore the effects of hyperbaric oxygen preconditioning (HBOP) on the permeability of blood-brain barrier (BBB) and expression of tight junction proteins under hypoxic conditions in vitro.MethodsA BBB in vitro model was constructed using the hCMEC/D3 cell line and used when its trans-endothelial electrical resistance (TEER) reached 80-120 Ω · cm2 (tested by Millicell-Electrical Resistance System). The cells were randomly divided into the control group cultured under normal conditions, the group cultured under hypoxic conditions (2%O2) for 24 h (hypoxia group), and the group first subjected to HBOP for 2 h and then to hypoxia (HBOP group). Occludin and ZO-1 expression were analyzed by immunofluorescence assay.ResultsNormal hCMEC/D3 was spindle-shaped and tightly integrated. TEER was significantly reduced in the hypoxia (P = 0.001) and HBOP group (P = 0.014) compared to control group, with a greater decrease in the hypoxia group. Occludin membranous expression was significantly decreased in the hypoxia group (P = 0.001) compared to the control group, but there was no change in the HBOP group. ZO-1 membranous expression was significantly decreased (P = 0.002) and cytoplasmic expression was significantly increased (P = 0.001) in the hypoxia group compared to the control group, although overall expression levels did not change. In the HBOP group, there was no significant change in ZO-1 expression compared to the control group.ConclusionHyperbaric oxygen preconditioning protected the integrity of BBB in an in vitro model through modulation of occludin and ZO-1 expression under hypoxic conditions.

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