Dehnshapiro2911

Accumulating evidence has indicated that circular RNAs (circRNAs) serve crucial roles in the progression of a diverse range of different types of cancer, including osteosarcoma (OS). The present study determined the expression pattern and function of circRNA homeodomain interacting protein kinase 3 (circHIPK3), a novel circular RNA, in OS. It was revealed that circHIPK3 expression was upregulated in OS tissue samples and OS cell lines. A localization assay revealed that circHIPK3 was primarily located in the cytoplasm. Using loss‑of‑function proliferation and Transwell assays, the present study revealed that circHIPK3‑knockdown suppressed OS cell proliferation, migration and invasion. Furthermore, the present study screened potential microRNAs that may interact with circHIPK3. It was revealed that microRNA‑637 (miR‑637) expression was downregulated in OS according to a Gene Expression Omnibus data analysis. In addition, the present study demonstrated that miR‑637 expression was downregulated in OS cell lines. A fluorescence in situ hybridization assay revealed that both miR‑637 and circHIPK3 were located in the cytoplasm. An in‑depth mechanism investigation demonstrated that circHIPK3 expression was inversely correlated with miR‑637 expression, and that circHIPK3 was a target of miR‑637. In addition, it was revealed that histone deacetylase 4 (HDAC4) was another downstream target gene of miR‑637, as demonstrated using a luciferase assay. It was revealed that miR‑637 suppressed OS cell proliferation, migration and invasion via targeting of HDAC4. Finally, the present study demonstrated that circHIPK3 sponged miR‑637 to promote HDAC4 expression and OS cell proliferation, migration and invasion. In conclusion, the present study uncovered the role of the circHIPK3/miR‑637/HDAC4 axis in OS cell proliferation, migration and invasion. It was demonstrated that circHIPK3 promoted OS cell proliferation, migration and invasion by modulating miR‑637/HDAC4 signaling.DEPTOR, an inhibitor of mammalian target of rapamycin (mTOR), is essential for the survival of multiple myeloma (MM) cells. The expression level of DEPTOR is closely related to the prognosis of patients with MM treated with the antiangiogenic agent thalidomide; however, its role in the regulation of angiogenesis has not yet been elucidated. In the present study, the expression levels of DEPTOR and vascular endothelial growth factor (VEGF), and the microvessel density (MVD) of bone marrow (BM) from patients with MM assessed. DEPTORoverexpression plasmid or CRISPR‑associated protein 9 (Cas9) and single guided RNAs (sgRNAs) were used to modulate DEPTOR expression. The DEPTOR‑mediated angiogenic effects were assessed using a tube formation assay of human umbilical vein endothelial cells (HUVECs) cultured in the collected conditioned medium from MM cell lines with different expression levels of DEPTOR. It was found that the expression level of DEPTOR negatively correlated with the VEGF level and BM MVD in MM. Autophagic activity was regulated by DEPTOR expression, but was not related to thalidomide‑binding protein CRBN, which is required for thalidomide to play an anti‑tumor and antiangiogenic role in MM cells. The disruption of DEPTOR protein decreased cellular autophagy, increased VEGF expression in MM cells, and inhibited the tube formation of HUVECs, while a high expression of DEPTOR exerted the opposite effect. Moreover, targeting DEPTOR also resulted in the production of mitochondrial reactive oxygen species (mtROS), the phosphorylation of nuclear factor‑κB (NF‑κB) and an increase in interleukin 6 (IL‑6) secretion. selleck inhibitor Of note, these effects are fully abrogated by treatment with autophagy activator (SMER28) or mitochondrial‑specific antioxidant (Mito‑TEMPO). Taken together, the present study demonstrates the role of DEPTOR in the regulation of autophagy/mtROS and subsequent angiogenesis. The results provide a novel mechanism for the further understanding of the therapeutic effects of thalidomide on MM.Induction of the apoptosis of tumor cells is a promising therapeutic approach for the treatment of cancer. Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) is a novel type of anticancer drug. However, gallbladder cancer cells (GBC) exhibit strong resistance to TRAIL. The aim of the present study was to assess the effect of rocaglate CR‑1‑31B (CR‑31), an inhibitor of eukaryotic translation initiation factor 4A (eIF4A), on the sensitization of cells to TRAIL‑induced apoptosis in TRAIL‑resistant GBC. eIF4A was highly abundant in GBC tissues and cell lines (GBC‑SD and SGC‑996). GBC cells were treated using TRAIL and/or CR‑31 and then apoptosis and TRAIL signaling were detected in vitro. CR‑31 enhanced the sensitivity of TRAIL‑resistant GBC cells, due to the CR‑31‑mediated eIF4A translational downregulation of c‑FLIP and the subsequent activation of the caspase cascade. Furthermore, GBC‑SD tumor xenografts models were established and the effects of CR‑31 in vivo were assessed. CR‑31 significantly reduced the growth and initiated the apoptosis of tumor cells, suggesting that CR‑31 also increased sensitivity in vivo. Taken together, the results of the present study show that CR‑31 treatment countered the resistance to TRAIL in GBC cells in vitro and in vivo. Therefore, eIF4A may serve as a novel therapeutic target and its combination with TRAIL‑CR‑31 as a therapy may serve as a novel strategy for GBC treatment.As a crucial transcription factor, sex‑determining region Y box 12 (SOX12) is closely related with tumorigenesis and malignant transformation in various malignant tumor types. To date, the specific function of SOX12 in esophageal squamous cell carcinoma (ESCC) has remained largely elusive and requires further investigation. The present study aimed to determine whether aberrant expression of SOX12 is associated with malignant development of ESCC. The expression level of SOX12 in ESCC cells and tissues was analyzed by RT‑qPCR and western blotting. Short hairpin RNA (shRNA) targeting SOX12 was transfected into ESCC cells to knock down the expression of SOX12. Colony formation and Transwell assays were used to detect viability and mobility of ESCC cells. Signaling pathway‑related proteins were assessed using western blot analysis and cellular immunofluorescence. Clinical prognosis data was analyzed by Kaplan‑Meier and Cox logistic regression. The present results revealed that SOX12 was overexpressed in ESCC cells and tissues.