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Emerging evidence has supported that TAZ (transcriptional co-activator with PDZ binding motif), one transcription co-activator in Hippo signaling pathway, plays an oncogenic role in liver carcinogenesis. Targeting TAZ could be a potential therapeutic approach for liver cancer patients. In the current study, we aim to determine whether diosgenin could be an inhibitor of TAZ in liver cancer cells. We found that diosgenin inhibited the expression of TAZ in liver cancer cells. Moreover, we found that diosgenin inhibited cell growth, induced apoptosis, suppressed cell migration and invasion in part via inhibition of TAZ in liver cancer cells. Our study provides the evidence to support that diosgenin could be a potential agent for treating human liver cancer. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common cancer disease with the second highest mortality. Circular RNAs (circRNAs) have been shown to play key roles in many tumors, including HCC. However, the function of circ_0000854 in the progression of HCC has not been clarified. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0000854, microRNA-1294 (miR-1294) and immunity related GTPase Q (IRGQ) in HCC cells and tissues. Western blot was used for protein expression analysis. Cell processes were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium Bromide (MTT) assay, thymidine analog 5-ethynyl-2′-deoxyuridine (EdU) assay, transwell assay, flow cytometry, and wound healing assay. Mechanically, the interaction of miR-1294 with circ_0000854 or IRGQ was notarized by dual-luciferase reporter assay and RNA pull-down assay. The xenotransplantation model was established to study the role of circ_0000854 in vivo. Circ_0000854 and IRGQ were highly expressed in HCC tissues and cells, while miR-1294 was downregulated. Silencing circ_0000854 suppressed HCC cell malignant behaviors, including proliferation, cell cycle progression, migration and invasion. Circ_0000854 exhibited sponge effect on miR-1294 and miR-1294 inhibition reversed function of circ_0000854 knockdown. In addition, miR-1294 targeted IRGQ and circ_0000854 sponged miR-1294 to upregulate IRGQ. Overexpression of IRGQ restored miR-1294-induced anti-tumor regulation in HCC cells. Animal experiments confirmed that silencing circ_0000854 inhibited tumor growth and metastasis of HCC via mediating miR-1294 and IRGQ levels in vivo. Circ_0000854 accelerated HCC progression via the miR-1294/IRGQ axis, providing a novel regulatory mechanism for HCC pathogenesis. • Circ_0000854 was highly expressed in HCC. • MiR-1294 was a target of circ_0000854, anti-miR-1294 restored the effect of sh-circ_0000854 on HCC cells. • IRGQ was a target of miR-1294. • Overexpression of IRGQ restored the inhibitory effect of miR-1294 overexpression on HCC cells growth. [ABSTRACT FROM AUTHOR]

Insulin, as a growth factor, can increase the risk of certain types of cancer. The present study showed that insulin promoted the proliferation of hepatocellular carcinoma cells in vitro and in vivo through pyruvate kinase M2 (PKM2), which is a rate-limiting enzyme in the process of glycolysis. Moreover, the expression of PKM2 was up-regulated by insulin at the posttranslational level in a nuclear orphan receptor TR3-dependent manner. In addition, insulin could enhance the interaction between PKM2 and TR3 and protect PKM2 from degradation. Our results identified a specific mechanism of insulin affecting cancer metabolism and thus promoting cancer progression, and they contribute to a better understanding of the observation that insulin is linked to an increased cancer risk under hyperinsulinemic conditions. • Insulin induced PKM2 expression. • Insulin enhanced the interaction between PKM2 with TR3 and protected PKM2 from degradation. • Insulin promoted the proliferation of hepatoma cells in vitro and vivo in a PKM2-dependant manner. [ABSTRACT FROM AUTHOR]

Increased angiogenesis in the liver plays a critical role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism underlying increased angiogenesis in HCC is not well understood. Current study was designed to identify the potential angiogenic effect of RNA-binding motif 4 (RBM4)through a small-scale overexpression screening, followed by comparison of the expression level of RBM4 in cancer and adjacent tissues in multiple malignancies to explore the relationship between RBM4 and CD31 protein expression level and related clinical indicators, and understand the role of RBM4 in the hepatocellular carcinoma. To understand the specific mechanism of RBM4 in detail, transcriptome sequencing, mass spectrometry and multiple molecular cytological studies were performed. These cellular level results were verified by experiments in animal models of nude mice. The increased expression of RBM4 in cancer tissues, suggested its use as a prognostic biomarker. The RBM4 expression was found to be strongly correlated with tumor microvessel density. Mechanistically, RBM4 mediated its effects via interaction with HNRNP-M through the latter's WDR15 domain, which then stabilized RelA/p65 mRNA. Consequently, RBM4 induced the activation of the NF-kB signaling pathway, upregulating the expression of proangiogenic factor VEGF-A. The results confirmed the mechanism by which RBM4 promotes angiogenesis in hepatocellular carcinoma suggesting RBM4 as a crucial promoter of angiogenesis in HCC, helping understand regulation of NF-kB signaling in HCC. [Display omitted] [ABSTRACT FROM AUTHOR]

Segetoside I is a plant-derived bisdesmosidic saponin from Vaccaria segetalis (Neck) with reported anticancer activities. This development has raised an interest in the therapeutic potential of segetoside I. Here, we report the in vitro and in vivo antitumor activities of segetoside I against some selected cancer cell lines (HepG2, human hepatoma; H 22 , mouse hepatoma; MCF-7, breast cancer; U251, gliocoma; BGC, HGC & SGC, gastric cancinoma; Lovo-1,colon cancer). MTT bioassay analysis showed that HepG2 cells were the most sensitive to segetoside I compared with other cancer cell lines, with lower toxicity in healthy mouse embryonic fibroblast cells. Segetoside I pretreatment of HepG2 resulted in apoptotic induction, dose-dependent DNA fragmentation, inhibition of cell migration, up-regulation of Bax and down-regulation of Bcl-2, which indicated that an apoptotic signaling event could have been initiated. The segetoside I also suppressed hepato-tumour growth in mice with virtually no cytotoxicity and prolonged animal survival, making it a strong oncology drug agent. These findings showed that segetoside I exhibited its antitumor activity via apoptotic induction and significantly support the possible application of the antitumor agent as a potential chemotherapeutic candidate worthy of further investigations. [ABSTRACT FROM AUTHOR]

Highlights: [•] miR-197 is negatively correlated with CD82 expressions in HCC cells and tissues. [•] miR-197 directly targets CD82. [•] Anti-miR-197 decreases both Rac1 and ROCK activities by mediating CD82 levels. [•] Anti-miR-197 suppresses HCC migration and invasion in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Highlights: [•] Ethyl pyruvate inhibits liver cancer. [•] Promotes apoptosis. [•] Decreased the expression of HMGB1, p-Akt. [Copyright &y& Elsevier]