Singletongrau0633

Liver cancer is the second leading cause of cancer‑related deaths. Traditional therapeutic strategies, such as chemotherapy, targeted therapy and interventional therapy, are inefficient and are accompanied by severe side effects for patients with advanced liver cancer. ND646 Therefore, it is crucial to develop a safer more effective drug to treat liver cancer. Veratramine, a known natural steroidal alkaloid derived from plants of the lily family, exerts anticancer activity in vitro. However, the underlying mechanism and whether it has an antitumor effect in vivo remain unknown. In the present study, the data revealed that veratramine significantly inhibited HepG2 cell proliferation, migration and invasion in vitro. Moreover, it was revealed that veratramine induced autophagy‑mediated apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway, which partly explained the underlying mechanism behind its antitumor activity. Notably, the results of in vivo experiments also revealed that veratramine treatment (2 mg/kg, 3 times a week for 4 weeks) significantly inhibited subcutaneous tumor growth of liver cancer cells, with a low systemic toxicity. Collectively, the results of the present study indicated that veratramine efficiently suppressed liver cancer HepG2 cell growth in vitro and in vivo by blocking the PI3K/Akt/mTOR signaling pathway to induce autophagic cell death. Veratramine could be a potential therapeutic agent for the treatment of liver cancer.Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE) are often used for palliative treatment of liver cancer. TAE and TACE can induce severe hypoxia. The present study investigated the effect of the myocardial infarction associated transcript (MIAT)/microRNA (miR)‑203a/hypoxia‑inducible factor 1‑α (HIF‑1α) axis on the therapeutic activity of TAE for liver cancer using hypoxia‑treated liver cancer cells and rat orthotopic liver tumors. MIAT, miR‑203a and HIF‑1α mRNA levels were assessed by reverse transcription‑quantitative PCR assay. The protein expression of HIF‑1α, Ki‑67 and vascular endothelial growth factor was determined by western blot assay. The proliferative, migratory and invasive potential of cells was assessed by CCK‑8, Transwell migration and invasion assays, respectively. The association between MIAT, miR‑203a and HIF‑1α was investigated through bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation and RNA pull‑down assay. In vivo experiments were performed to explore the effect of TAE alone or in combination with MIAT knockdown on the growth of rat liver tumors. The results revealed that MIAT and HIF‑1α were highly expressed, and miR‑203a was lowly expressed in liver tumors of patients with liver cancer after TACE treatment and hypoxia‑stimulated liver cancer cells. MIAT sequestered miR‑203a from its target HIF‑1α. MIAT knockdown, miR‑203a overexpression or HIF‑1α loss inhibited proliferation, migration and invasion in hypoxia‑treated liver cancer cells. MIAT knockdown enhanced TAE‑mediated antitumor effects by upregulating miR‑203a and downregulating HIF‑1α in rat liver tumors. In conclusion, MIAT knockdown potentiated the therapeutic effect of TAE in liver cancer by regulating the miR‑203a/HIF‑1α axis in vitro and in vivo, thus expanding our understanding on the function and molecular basis of MIAT in TAE treatment for liver cancer.The expression levels of microRNA (miR)‑340‑5p are reportedly decreased in the peripheral blood during acute ischemic stroke; however, the direct effect and mechanism of action of miR‑340‑5p in ischemic stroke remains largely unknown. The present study aimed to investigate the effects of miR‑340‑5p, and its mechanism of action, on PC12 cells following oxygen‑glucose deprivation/reperfusion (OGD/R) induction. OGD/R‑induced PC12 cells served as the cellular model and subsequently, mRNA expression levels of miR‑340‑5p and neuronal differentiation 4 (Neurod4) were analyzed using reverse transcription‑quantitative PCR. Tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 expression levels were detected using ELISA kits, and flow cytometry was used to determine the rate of cellular apoptosis. In addition, a nitric oxide (NO) synthase activity assay kit was used to detect NO levels and a NADPH assay kit was used to measure NADPH levels. Western blotting was also performed to analyze protein expression levels of bax, bcl‑2, cleaved caspase 3 and phosphorylated endothelial NOS (eNOS), and the target gene of miR‑340‑5p was predicted using TargetScan software and verified using a dual‑luciferase reporter assay. The expression levels of miR‑340‑5p were decreased in PC12 cells following OGD/R induction and Neurod4 was identified as a target gene of miR‑340‑5p. In addition, miR‑340‑5p overexpression reduced inflammation, apoptotic rate, NO production and NADPH levels, in addition to increasing eNOS expression in PC12 cells following OGD/R induction. Notably, the overexpression of Neurod4 reversed the aforementioned effects of miR‑340‑5p on PC12 cells following OGD/R induction. In conclusion, the findings of the present study suggested that miR‑340‑5p may protect PC12 cells against OGD/R through targeting Neurod4, which could provide important implications for the treatment of ischemia‑reperfusion injury based on miR‑340‑5p expression levels in vivo.The aim of the present study was to investigate the expression of spalt like transcription factor 4 (SALL4) in the three most common types of renal cell carcinomas (RCC) [clear cell RCC (ccRCC), papillary renal cell carcinoma (pRCC) and chromophobe RCC (chRCC)], and the association with the overall survival (OS) of patients. The Cancer Genome Atlas (TCGA) database and RCC samples were used to investigate the expression levels of the SALL4 gene and its association with the OS in the three types of RCC based on the analysis of the transcriptome, copy number and survival data. It was found that SALL4 was highly expressed in ccRCC and pRCC tumor tissue, and low mRNA expression level of SALL4 indicated a prolonged survival in both ccRCC and pRCC. This mRNA expression level was associated with pathological Tumor‑Node‑Metastasis stage, M and T stages in both ccRCC and pRCC. The analysis of the enriched pathway results suggested that SALL4 may act via translation initiation, and that the related genes promoted the progression of RCC.