Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway.

Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.

[Retracted] Long noncoding RNA UCID sponges miR­152­3p to promote colorectal cancer cell migration and invasion via the Wnt/ß­catenin signaling pathway.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that there appeared to be matching data panels comparing between the Transwell invasion and migration assays shown in Figs. 2C and 5C; moreover, one of the data panels shown in Fig. 2D had previously appeared in a paper written largely by different authors (the author 'T­D Shan' was held in common) at different research institutes in the journal Oncotarget in 2016 [Shan T­D, Xu, J­H, Yu T, Li J­Y, Zhao L­N, Ouyang H, Luo S, Lu X­J, Huang C­Z, Lan Q­S et al: Knockdown of linc­POU3F3 suppresses the proliferation, apoptosis, and migration resistance of colorectal cancer. Oncotarget 7: 961­975, 2016]. Finally, an independent investigation of these data in the Editorial Office revealed that, in addition to the data shared between Figs. 2 and 5, there were overlapping data panels both within Fig. 5C and within the wound healing assay data shown in Fig. 3B. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, and given the number of cases of overlapping data panels both within and between figures in the artce itself, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they did not agree with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 44: 1194­1295, 2020; DOI: 10.3892/or.2020.7670].

Long noncoding RNA UCID sponges miR­152­3p to promote colorectal cancer cell migration and invasion via the Wnt/ß­catenin signaling pathway.

Research has shown that long noncoding RNAs (lncRNAs) play significant roles in colorectal cancer (CRC). However, the role of lnc­UCID (lncRNA upregulating CDK6 by interacting with DHX9) in CRC remains largely unknown. In the present study, analyses revealed that lnc­UCID was markedly upregulated in CRC compared with that in normal specimens. Functional experiments showed that the depletion of lnc­UCID inhibited CRC cell invasion and migration significantly, while overexpression of lnc­UCID had the opposite effect. A candidate target of lnc­UCID, microRNA miR­152­3p, was identified using bioinformatic analysis. Moreover, in CRC tissue, we noted an inverse correlation between miR­152­3p and lnc­UCID expression levels. Overexpression and knockdown experiments revealed opposing roles for miR­152­3p and lnc­UCID, suggesting that lnc­UCID negatively regulates miR­152­3p. Luciferase reporter assays demonstrated that miR­152­3p directly targets lnc­UCID. The results suggest that lnc­UCID acts as an endogenous miRNA sponge, competing for miR­152­3p binding and thereby regulating the miRNA's targets. Overall, we propose that the lnc­UCID/miR­152­3p/Wnt/ß­catenin signaling axis represents a novel mechanism that explains the migration and invasion of CRC.

Acidic stress induces protective autophagy in SGC7901 cells.

Objective To investigate the effect of acidity on gastric cancer SGC7901 cells in terms of autophagy and provide a new strategy for therapeutically targeting gastric cancer autophagy in an acidic environment. Methods Transmission electron microscopy (TEM) and confocal laser scanning microscopy were used to examine the effect of an acidic environment on autophagosome formation. Light chain 3 (LC3) and p62 levels in SGC7901 cells exposed to acidic conditions were measured using Western blot analysis. To explore changes in autophagy flux, the cells were treated with an inhibitor of autophagy bafilomycin A1. The CCK-8 assay was performed to determine if inhibiting acid-induced autophagy affected cell proliferation. Results Increased autophagosome formation was observed by TEM. Punctate LC3 structures were observed in cells cultured under acidic conditions, whereas untreated cells exhibited diffuse and weak staining for punctate LC3 structures. Cytoplasmic LC3-I translocated to the autophagic membrane (LC3-II) levels increased under acidic conditions, whereas p62 levels decreased. The bafilomycin A1-induced inhibition of autophagy caused by the acidic environment inhibited cell proliferation. Conclusion The acidic environment upregulates autophagy in SGC7901 cells. In long-term culture, a stable and high level of autophagy is maintained in an acidic environment, which has a protective effect on cells.

Tspan9 inhibits the proliferation, migration and invasion of human gastric cancer SGC7901 cells via the ERK1/2 pathway.

Tetraspanins are a heterogeneous group of 4-transmembrane proteins that recruit other cell surface receptors and signaling proteins into tetraspanin-enriched microdomains (TEMs). TEMs of various types are involved in the regulation of cell growth, migration and invasion of several tumor cell types, both as suppressors or promotors. Tetraspanin 9 (Tspan9, NET-5, PP1057), a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins, reportedly regulates platelet function in concert with other platelet tetraspanins and their associated proteins. Our previous study demonstrated that Tspan9 is also expressed in gastric cancer (GC), but the role of Tspan9 in GC has not been well characterized. In this study, we investigated the influence of Tspan9 on proliferation, migration and invasion of human gastric cancer SGC7901 cells using CCK-8 assay, cell cycle analysis, wound-healing assay and Transwell assay. Western blot analysis and ELISA assay were also performed to identify the potential mechanisms involved. The proliferation, migration and invasion of human gastric cancer SGC7901 cells were significantly inhibited by overexpression of Tspan9. In addition, Tspan9 downregulated the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and the secretion levels of proteins related to tumor metastasis, such as matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA). Our study indicated that Tspan9 inhibited SGC7901 cell proliferation, migration and invasion through the ERK1/2 pathway.

[Effects of naloxone on the contents of cAMP in hypothalamus and AVP in ventral septal area in fever rats].

AIM: To study the effects and mechanism of naloxone on the febrile response in IL-1beta-induced fever rats. METHODS: The fever model was established by intracerebroventricular injection of IL-1beta in rats. The effect of naloxone on the body temperature of feverrats was observed. The contents of cAMP in hypothalamus and AVP in VSA were detected. RESULTS: Naloxone alleviated IL-1beta-induced fever and the contents of cAMP in hypothalamus and AVP in VSA were correspondingly decreased (P < 0.01). CONCLUSION: Naloxone could inhibit IL-1beta-induced fever in rats, and the mechanism might be due to inhibiting synthesis of cAMP in hypothalamus and promoting release of AVP in VSA.