Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy.

Malignant glioma is an aggressive brain cancer that responds poorly to chemotherapy. However, the molecular mechanism underlying the development of chemoresistance in glioma is not well-understood. In this study, we show that long non-coding RNA AC023115.3 is induced by cisplatin in human glioblastoma cells and that elevated AC023115.3 promotes cisplatin-induced apoptosis by inhibiting autophagy. Further mechanistic studies revealed that AC023115.3 acts as a competing endogenous RNA for miR-26a and attenuates the inhibitory effect of miR-26a on GSK3β, a proline-directed serine-threonine kinase that promotes the degradation of Mcl1, leading to an increase in GSK3β and a decrease in autophagy. Additionally, we discovered that AC023115.3 improves chemosensitivity of glioma cells to cisplatin by regulating the miR-26a-GSK3β-Mcl1 pathway. Thus, these data indicate that the AC023115.3-miR-26a-GSK3β signalling axis plays an important role in reducing the chemoresistance of glioma.

The unfolded protein response (UPR), which is activated by perturbations of the endoplasmic reticulum homeostasis, has been shown to play an important role in innate immunity and inflammation. However, little is known about the molecular mechanisms underlying activation of the UPR during immune responses. Using small RNA deep sequencing and reverse genetic analysis, we show that the microRNA mir-233 is required for activation of the UPR in Caenorhabditis elegans exposed to Pseudomonas aeruginosa PA14. P. aeruginosa infection up-regulates the expression of mir-233 in a p38 MAPK-dependent manner. Quantitative proteomic analysis identifies SCA-1, a C. elegans homologue of the sarco/endoplasmic reticulum Ca2+-ATPase, as a target of mir-233. During P. aeruginosa PA14 infection, mir-233 represses the protein levels of SCA-1, which in turn leads to activation of the UPR. Whereas mir-233 mutants are more sensitive to P. aeruginosa infection, knockdown of sca-1 leads to enhanced resistance to the killing by P. aeruginosa. Our study indicates that microRNA-dependent pathways may have an impact on innate immunity by activating the UPR.

Polydopamine (PDA) capsule and core-shell structures with tailored structures and properties are of particular interests due to their multifunctions and potential applications as new colloidal structures in diverse¯elds. Among the available fabrication methods, PDA¯lm onto colloidal particles followed by selective template removal has attracted extensive attention due to its advantages of precise control over the size, wall thickness and functions of the obtained capsules. The past several years has witnessed a rapid increase of research concerning the new fabrication strategies, functionalization and applications of this kind of capsules and core-shell structures, particularly in many¯elds such as drug delivery, catalysis, antibacterial, etc. In this review, the very recent progress of the capsule and core-shell structures based on PDA are summarized. There are basically two sections, including the fabrication process of PDA capsules, core-shell structures, and the various applications based on PDA.

The proneural (PN) and mesenchymal (MES) subtypes of glioblastoma multiforme (GBM) are robust and generally consistent with classification schemes. GBMs in the MES subclass are predominantly primary tumors that, compared to PN tumors, exhibit a worse prognosis; thus, understanding the mechanism of MES differentiation may be of great benefit for the treatment of GBM. Nuclear factor kappa B (NF-κB) signaling is critically important in GBM, and activation of NF-κB could induce MES transdifferentiation in GBM, which warrants additional research. NUDT21 is a newly discovered tumor-associated gene according to our current research. The exact roles of NUDT21 in cancer incidence have not been elucidated. Here, we report that NUDT21 expression was upregulated in human glioma tissues and that NUDT21 promoted glioma cell proliferation, likely through the NF-κB signaling pathway. Gene set enrichment analysis, western blotting, and quantitative real-time reverse transcription polymerase chain reaction confirmed that NF-κB inhibitor zeta (NFKBIZ) was a downstream target affected by NUDT21 and that the MES identity genes in glioblastoma cells, CHI3L1 and FN1, were also differentially regulated. Our results suggest that NUDT21 is an upstream regulator of the NF-κB pathway and a potential molecular target for the MES subtype of GBM.

Effects of sevoflurane and propofol anesthesia on pulmonary function, matrix metalloproteinase-9 (MMP-9) and postoperative cognition were compared in patients undergoing simple resection of lower lobe of left lung. Retrospective method was used to analyze 58 cases of lung cancer patients treated by simple resection of lower lobe of left lung in the Second Hospital of Dalian Medical University from October 2016 to October 2017, and they were divided into two groups: Sevoflurane group (n=32) with sevoflurane anesthesia and propofol group (n=26) with propofol anesthesia. In the present study, the moment before induction of anesthesia (T1), before the start of one-lung ventilation (T2), before the end of one-lung ventilation (T3), after closed chest surgery (T4), 24 h after surgery (T5), calculate alveolar-arterial oxygen difference (A-aDO2), respiratory index (RI) and intrapulmonary shunt ratio (Qs/Qt), were compared between the two groups. The serum MMP-9 concentration at T1, T4 and T5 were detected by enzyme linked immunosorbent assay. The cognitive function of two groups was assessed by Mini-Mental State Examination (MMSE) 1 day before surgery and 1 and 10 days after surgery. The A-aDO2 level at T4 in sevoflurane group was significantly higher than that in propofol group (P<0.05). The RI level at T3, T4, the Qs/Qt and the MMP-9 level at T4 in the sevoflurane group was significantly higher than that in the propofol group (P<0.05). The MMSE score in sevoflurane group was significantly lower than that in propofol group 1 and 10 days after surgery (P<0.05). Propofol has little effect on pulmonary function and can decrease inflammatory factor MMP-9. Both sevoflurane and propofol have an effect on cognitive function after lung cancer resection, but propofol can reduce cognitive impairment in patients with lung cancer.

Hepatocellular carcinoma (HCC) is a highly aggressive carcinoma worldwide. Circular RNAs (circRNAs) have been proved to be involved in the pathogenesis of several carcinomas. circ_0000267 was reported to be elevated in HCC tissue samples by circRNA microarray. In this study, quantitative reverse-transcription polymerase chain reaction was induced to further detect the expression of circ_0000267 in HCC tissues and cells. The clinical significance was also explored by Fisher's exact test, Kaplan-Meier curves and Cox regression analysis. Cell counting kit-8, colony formation, flow cytometry and transwell experiments were conducted on HCC cells to elucidate the functions of circ_0000267. Dual-luciferase reporter assay was induced to explore the mechanism of circ_0000267. Moreover, rescue experiments were also performed on HCC cells. As a result, circ_0000267 was enhanced in HCC tissues and cell lines. This upregulation is associated with patients' clinical severity and poor prognosis. Functionally, circ_0000267 could facilitate cell growth, migration and invasion and attenuate cell apoptosis in HCC cells. Mechanistically, circ_0000267 could directly sponge miR-646 to exert its oncogenic properties. In summary, we identified a novel HCC-associated circRNA in the progression of this fatal disease. K E Y W O R D S circ_0000267, circular RNA, hepatocellular carcinoma, miR-646, prognosis How to cite this article: Pan H, Tang L, Jiang H, et al. Enhanced expression of circ_0000267 in hepatocellular carcinoma indicates poor prognosis and facilitates cell progression by sponging miR-646.

Our previous study demonstrated that nano nickel oxide (NiO) induce pulmonary fibrosis in rats and collagen excessive formation in A549 cells, which mechanism was related with the increasing transforming growth factor β1 (TGF‐β1) secretion. However, it remains unclear understanding the role of TGF‐β1 in collagen excessive formation. Here, we found nano NiO could directly promote epithelial‐mesenchymal transition (EMT) via the TGF‐β1/Smads pathway in A549 cells. First, cytotoxicity induced by nano NiO has a dose‐ and time‐dependent manner according to methylthiaozol tetrazolium assay. Second, nano NiO led to the increased contents of type I collagen (Col‐I), TGF‐β1, p‐Smad2, p‐Smad3, alpha‐smooth muscle actin (α‐SMA), vimentin, and fibronectin, indicating Smads pathway activation and EMT occurence. Third, to verify whether TGF‐β1 activated Smads signaling pathway and EMT occurence, A549 cells were exposed to nano NiO and TGF‐β1 inhibitors (10 μM SB431542). The results showed that TGF‐β1 inhibitors alleviated the nano NiO‐induced cytotoxicity and Col‐I excessive formation. Meanwhile, TGF‐β1 inhibitors reversed the proteins expression trends of Col‐I, p‐Smad2, p‐Smad3, α‐SMA, vimentin, fibronectin, and E‐cadherin. These observations suggested that EMT occurrence via TGF‐β1/Smads pathway might play an important role in the collagen excessive formation induced by nano NiO in A549 cells.