Robertsmcdaniel2604

Blocking autophagy flux with the final stage autophagy inhibitor chloroquine (CQ) also upregulated DR4 and DR5 expression. TRAIL in combination with amitriptyline or CQ significantly increased the expression of apoptosis‑indicator proteins cleaved caspase‑8 and caspase‑3. The expression levels of LC3‑II and p62 were significantly higher in amitriptyline‑treated cells, which confirmed that amitriptyline blocks autophagy by inhibiting the fusion of autophagosomes with lysosomes. Overall, the present results contributed to understanding the mechanism responsible for the synergistic anticancer effect of amitriptyline and TRAIL and also presented a novel mechanism involved in DR4 and DR5 upregulation.Aberrant expression of circular RNAs (circRNAs) has been demonstrated to be related to the development of colorectal cancer (CRC), the third most common cancer worldwide. However, the mechanism of the effect of circRNA NOP2/Sun domain family, member 2 (circNSUN2) on the malignant biological behavior of CRC remains unclear. In the present study, the expression of circNSUN2 and microRNA (miR)‑181a‑5p was detected by RT‑qPCR. The expression of Rho‑associated coiled‑coil‑containing protein kinase 2 (ROCK2) was measured by western blotting. Cell proliferation was detected by CCK‑8 assay. The cell apoptosis rate was measured by flow cytometry. Cell migration ability was evaluated by Transwell assay. The interactions between circNSUN2, miR‑181a‑5p and ROCK2 were verified by dual‑luciferase reporter assay. The results revealed that circNSUN2 was highly expressed in CRC tissues and cell lines. Knockdown of circNSUN2 inhibited the malignant biological behavior of CRC in vivo and in vitro. Moreover, miR‑181a‑5p was revealed to be a target gene of circNSUN2, and the expression of ROCK2 was negatively regulated by miR‑181a‑5p. Knockdown of circNSUN2 inhibited proliferation and migration, and induced apoptosis of CRC cells and suppressed tumor growth by targeting miR‑181a‑5p to decrease ROCK2 expression. In conclusion, circNSUN2 promoted the progression of CRC by sponging miR‑181a‑5p to increase the expression of ROCK2.Nasopharyngeal carcinoma (NPC) is a common malignant tumor in South China and is characterized by a high death rate. Ophiopogonin B (OP‑B) is a bioactive component of Radix Ophiopogon japonicus, which is frequently used in traditional Chinese medicine to treat cancer. The present study aimed to examine the anti‑cancer properties of OP‑B on NPC cells. Cell viability and cell proliferation were measured using MTT and EdU assays. Flow cytometry was used to measure cell apoptosis, reactive oxygen species and mitochondrial membrane potential. Western blotting was used to investigate the expression of apoptosis and Hippo signaling pathway proteins. OP‑B inhibited the proliferation of NPC cells by inducing apoptosis and disturbing the mitochondrial integrity. OP‑B enhanced ROS accumulation. In addition, OP‑B promoted the expression of mammalian STE20‑like kinase 1, large tumor suppressor 1 and phosphorylated yes‑associated protein (YAP) and suppressed the expression of YAP and transcriptional enhanced associate domain in NPC cells. OP‑B increased the expression of forkhead box transcription factor O1 in the nuclear fraction. In conclusion, OP‑B has therapeutic potential and feasibility in the development of novel YAP inhibitors for NPC.Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Figs. 4C, 5B and 6D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 34 2202‑2210, 2015; DOI 10.3892/or.2015.4165].Following the publication of this paper, the authors have realized that they overlooked indicating that Zhikun Chen and Qin Che contributed equally to this work. Therefore, the affiliations for this paper should have been written as follows Zhikun Chen1*, Qin Che2* and Chunxue Xie3. Departments of 1Emergency, 2Infectious Diseases and 3General Practice, Jingmen No. 1 People's Hospital, Jingmen, Hubei 448000, P.R. China. *Contributed equally. The authors confirm that there are no further errors in the study, and all the authors agree to this correction. The authors regret their oversight, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 23 Article no. 111, 2021; DOI 10.3892/mmr.2020.11750].Skeletal muscle atrophy is a common feature of patients suffering with chronic infection and other systemic diseases, including acquired immunodeficiency syndrome, chronic kidney disease and cancer. Therefore, understanding the molecular basis of muscle loss is of importance. The majority of members of the forkhead box O (FoxO) family can induce skeletal muscle atrophy; however, the effect of FoxO6 on skeletal muscle is not completely understood. The present study investigated the role of FoxO6 in vitro and in vivo. Compared with the small interfering RNA (si)‑negative control (NC) group, C2C12 cell proliferation (Cell Counting Kit‑8 assay), myotube differentiation and myotube production were significantly decreased by FoxO6 knockdown, which was different from the known functions of other FoxO members. The immunofluorescence assay results demonstrated that si‑FoxO6 clearly downregulated the expression levels of myosin heavy chain (MyHC) in C2C12 myotubes compared with si‑NC. The western blotting results indicated that compared with the si‑NC group, FoxO6 knockdown induced C2C12 myotube atrophy by notably downregulating myoblast determination protein 1 (MyoD), mTOR and MyHC expression levels, and by markedly upregulating ubiquitin ligase (atrogin1) and muscle RING‑finger protein‑1 (MURF1) expression levels. Similarly, in an in vitro model of TNF‑α‑induced myotube atrophy, the western blotting results indicated that FoxO6 expression levels were decreased, whereas atrogin1, MURF1, FoxO1 and FoxO3a expression levels were increased compared with the control group. Therefore, the results indicated that, unlike FoxO1 or FoxO3a, FoxO6 maintained C2C12 myotubes and protected against atrophy. Consistent with the in vitro data, similar results were observed in vivo. Collectively, the results of the present study suggested that FoxO6 served a critical role in muscle cell metabolism in vitro and in vivo, and might serve as a promising therapeutic target for ameliorating skeletal muscle atrophy.Increasing evidence has demonstrated that regulatory T cells (Tregs) suppress innate immunity, as well as protect the kidneys from ischemia‑reperfusion injury (IRI) and offer a potentially effective strategy to prevent or alleviate renal IRI. The present study explored whether C‑X‑C motif chemokine receptor 3 (CXCR3) alleviated renal IRI by increasing Tregs. Male C57BL/6J mice were divided into sham‑surgery, IRI, CXCR3 overexpression (OE‑CXCR3)+IRI, PC61+IRI and OE‑CXCR3+PC61+IRI groups. selleck Histopathological examination of the kidney was carried out using hematoxylin‑eosin and Masson staining. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Blood and kidney levels of IL‑6, TNF‑α, C‑C motif chemokine ligand (CCL)‑2 and IL‑10 were detected by ELISA and western blotting. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px) and malondialdehyde (MDA) in kidney tissues were also measured to assess oxidative stress. The population of Tregs in the kidney was assessed using flow cytometry. The results demonstrated that administration of OE‑CXCR3 to IRI mice significantly decreased the levels of Scr, BUN, IL‑6, TNF‑α, CCL‑2 and MDA, increased the levels of IL‑10, SOD and GSH‑Px, and mitigated the morphologic injury and fibrosis induced by IR compared with the IRI group. In addition, administration of OE‑CXCR3 induced significant reductions in the expression levels of fibrosis‑related markers, including fibronectin and type IV collagen, and increased the number of Tregs. These roles of OE‑CXCR3 were significantly neutralized following deletion of Tregs with PC61 (anti‑CD25 antibody). Together, the present study demonstrated that injection of OE‑CXCR3 lentiviral vectors into animal models can alleviate renal IRI by increasing the number of Tregs. The results may be a promising approach for the treatment of renal IRI.Multidrug resistance (MDR) is one of the major reasons for the clinical failure of cancer chemotherapy. Autophagy activation serves a crucial role in MDR. However, the specific molecular mechanism linking autophagy with MDR remains unknown. The results of the present study demonstrated that autophagy was inhibited and microRNA (miR)‑199a‑5p levels were upregulated in MDR model lung cancer cells (A549/T and H1299/T) compared with those in the parental cell lines. Paclitaxel (PTX) treatment increased the expression levels of miR‑199a‑5p in parental lung cancer cells compared with those in PTX‑untreated cells, and these expression levels were negatively correlated with PTX sensitivity of the cells. miR‑199a‑5p knockdown in A549/T cells induced autophagy and resensitized cells to multiple chemotherapeutic drugs including PTX, taxotere, topotecan, SN38, oxaliplatin and vinorelbine. By contrast, miR‑199a‑5p overexpression in A549 cells suppressed autophagy and desensitized cells to these chemotherapeutic drugs. Mechanistically, the results of the present study demonstrated that miR‑199a‑5p blocked autophagy by activating the PI3K/Akt/mTOR signaling pathway and inhibiting the protein expression of autophagy‑related 5. Furthermore, p62 protein was identified as a direct target of miR‑199a‑5p; miR‑199a‑5p bound to p62 mRNA to decrease its mRNA and protein expression levels. In conclusion, the results of the present study suggested that miR‑199a‑5p may contribute to MDR development in lung cancer cells by inhibiting autophagy and targeting p62. The regulatory effect of miR‑199a‑5p on autophagy may provide novel insights for future multidrug‑resistant lung cancer chemotherapy.Transforming growth factor‑β1 (TGF‑β1)‑induced epithelial‑mesenchymal transition (EMT) serves a significant role in pulmonary fibrosis (PF). Increasing evidence indicates that microRNAs (miRNAs or miRs) contribute to PF pathogenesis via EMT regulation. However, the role of miR‑483‑5p in PF remains unclear. Therefore, the present study investigated the potential effect of miR‑483‑5p on TGF‑β1‑induced EMT in PF. It was found that the expression of miR‑483‑5p was upregulated in both PF tissue and A549 cells treated with TGF‑β1, whereas expression of Rho GDP dissociation inhibitor 1 (RhoGDI1) was downregulated. miR‑483‑5p mimic transfection promoted TGF‑β1‑induced EMT; by contrast, miR‑483‑5p inhibitor inhibited TGF‑β1‑induced EMT. Also, miR‑483‑5p mimic decreased RhoGDI1 expression, whereas miR‑483‑5p inhibitor increased RhoGDI1 expression. Furthermore, dual‑luciferase reporter gene assay indicated that miR‑483‑5p directly regulated RhoGDI1. Moreover, RhoGDI1 knockdown eliminated the inhibitory effect of the miR‑483‑5p inhibitor on TGF‑β1‑induced EMT via the Rac family small GTPase (Rac)1/PI3K/AKT pathway.