The microRNA-371-373 (miR-371-373) cluster is specifically expressed in human embryonic stem cells (ESCs) and is thought to be involved in stem cell maintenance. Recently, microRNAs (miRNAs) of this cluster were shown to be frequently upregulated in several human tumors. However, the regulatory mechanism for the involvement of the miR-371-373 cluster in human ESCs or cancer cells remains unclear. In this study, we explored the relationship between this miRNA cluster and the Wnt/β-catenin-signaling pathway, which has been shown to be involved in both stem cell maintenance and tumorigenesis. We show that miR-371-373 expression is induced by lithium chloride and is positively correlated with Wnt/β-catenin-signaling activity in several human cancer cell lines. Mechanistically, three TCF/LEF1-binding elements (TBEs) were identified in the promoter region and shown to be required for Wnt-dependent activation of miR-371-373. Interestingly, we also found that miR-372&373, in turn, activate Wnt/β-catenin signaling. In addition, four protein genes related to the Wnt/β-catenin-signaling pathway were identified as direct targets of miR-372&373, including Dickkopf-1 (DKK1), a well-known inhibitor of Wnt/β-catenin signaling. Using a lentiviral system, we showed that overexpression of miR-372 or miR-373 promotes cell growth and the invasive activity of tumor cells as knockdown of DKK1. Taken together, our study demonstrates a novel β-catenin/LEF1-miR-372&373-DKK1 regulatory feedback loop, which may have a critical role in regulating the activity of Wnt/β-catenin signaling in human cancer cells.

Dopamine receptors are belong to the family of G protein-coupled receptor. There are five types of dopamine receptor (DR), including DRD1, DRD2, DRD3, DRD4, and DRD5, which are divided into two major groups: the D1-like receptors (DRD1 and DRD5), and the D2-like receptors (DRD2, DRD3, and DRD4). Dopamine receptors are involved in all of the physiological functions of dopamine, including the autonomic movement, emotion, hormonal regulation, dopamine-induced immune effects, and tumor behavior, and so on. Increasing evidence shows that dopamine receptors are associated with the regulation of tumor behavior, such as tumor cell death, proliferation, invasion, and migration. Recently, some studies showed that dopamine receptors could regulate several ways of death of the tumor cell, including apoptosis, autophagy-induced death, and ferroptosis, which cannot only directly affect tumor behavior, but also limit tumor progress via activating tumor immunity. In this review, we focus mainly on the function of the dopamine receptor on Bio-behavior of tumor as a potential therapeutic target.

Lenvatinib is the latest and promising agent that has demonstrated a significant improvement of progression-free survival in advanced hepatocellular carcinoma (HCC). However, resistance emerges soon after initial treatment, limiting the clinical benefits of lenvatinib. Therefore, understanding the mechanism of resistance is necessary for improving lenvatinib efficacy. YRDC promotes the proliferation of hepatocarcinoma cells via regulating the activity of the RAS/RAF/MEK/ERK pathway, which was the primary pathway of the anticancer effect of lenvatinib. The purpose of this study is to investigate whether YRDC modulates the sensitivity of lenvatinib in hepatocarcinoma cells. Using the CCK-8 cell viability assay, wound-healing assay and clone formation assay in cell models, and xenograft assay in null mouse, we demonstrated that Huh7 cells with YRDC knockdown showed decreased susceptibility to lenvatinib than their control cells. Furthermore, we found that lenvatinib inhibited the expression of YRDC in a time-dependent manner. This effect may aggravate resistance to lenvatinib in hepatocarcinoma cells and may be an underlying cause of resistance, which emerges soon after lenvatinib initial treatment. To investigate how YRDC modulates the sensitivity of lenvatinib, we assessed the effect of tRNA with different t6A levels on the translation of the KRAS gene by in vitro rabbit reticulocyte translation system and measured the expression levels of the KRAS gene by western blot together with qPCR. We found that YRDC regulates the protein translation of KRAS in cell models, and the tRNA with low t6A modification level reduces the translation of the KRAS in the in vitro translation system. These results suggested that YRDC mediates the resistance of lenvatinib in hepatocarcinoma cells via modulating the translation of the KRAS. In this study, YRDC was confirmed to be a potential novel predictive biomarker of lenvatinib sensitivity in HCC.

Shaoyao-Gancao-Tang (SGT) is a traditional Chinese prescription containing Radix Paeoniae alba and Radix Glycyrrhizae and is commonly used to relieve pains. Albiflorin and paeoniflorin are the main effective compounds of Radix Paeoniae alba, and the pharmacokinetic differences of the two compounds in rats after oral administration of SGT and single herb Paeony decoction were studied. At different time points (5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, and 540 min) after administration, plasma concentrations of albiflorin and paeoniflorin were determined using a simple and reliable UPLC method, and main pharmacokinetic parameters were evaluated. It was found that there were significant differences (p < 0.05 or p < 0.01) between the two groups. The results indicated that some components in the other ingredient herb of SGT (Radix Glycyrrhizae) had a pharmacokinetic interaction with albiflorin and paeoniflorin and hence reduced their systematic exposure level.

The composition and variability of the terpenes and their derivatives isolated from the needles of a representative pool of 114 adult trees originating from four natural populations of dwarf mountain pine (Pinus mugo Turra) from the Julian Alps were investigated by GC‐FID and GC/MS analyses. In total, 54 of the 57 detected essential‐oil components were identified. Among the different compound classes present in the essential oils, the chief constituents belonged to the monoterpenes, comprising an average content of 79.67% of the total oil composition (74.80% of monoterpene hydrocarbons and 4.87% of oxygenated monoterpenes). Sesquiterpenes were present in smaller amounts (average content of 19.02%), out of which 16.39% were sesquiterpene hydrocarbons and 2.62% oxygenated sesquiterpenes. The most abundant components in the needle essential oils were the monoterpenes δ‐car‐3‐ene, β‐phellandrene, α‐pinene, β‐myrcene, and β‐pinene and the sesquiterpene β‐caryophyllene. From the total data set of 57 detected compounds, 40 were selected for principal‐component analysis (PCA), discriminant analysis (DA), and cluster analysis (CA). The overlap tendency of the four populations suggested by PCA, was as well observed by DA. CA also demonstrated similarity among the populations, which was the highest between Populations I and II.

Background This study explored the diagnostic power of preoperative circulating tumor cells (CTCs) for the presence of microvascular invasion (MVI) and the relationship between dynamic changes in postoperative CTCs and prognosis. Methods A total of 137 patients were recruited for the study. Preoperative blood samples were collected from all patients to detect CTCs. The time points for blood collection were before the operation, during the operation, and at 1 week, 1 month, 2 months, 3 months, 6 months, and 1 year after surgery. The predictive power of CTC count for the presence of MVI was analyzed by receiver operating characteristic (ROC) curve analysis. According to recurrence status, 137 patients were divided into three groups: no recurrence, early recurrence, and non-early recurrence groups. Results A threshold CTC count of 5 showed the most significant power for predicting the existence of MVI. In multivariate analysis, the parameters of preoperative CTC count, alpha-fetoprotein (AFP) and tumor diameter were independent predictors of MVI (P <  0.05). A CTC count greater than or equal to 5 had better predictive value than AFP > 400 μg/L and tumor diameter > 5 cm. The number of intraoperative CTCs in the three groups did not increase compared to that before surgery (P > 0.05). The number of CTCs in the nonrecurrence group and the non-early recurrence group decreased significantly 1 week after surgery compared with the intraoperative values (P <  0.001), although there was no significant difference in the early recurrence group (P = 0.95). Patients with mean CTC count ≥5 had significantly worse long-term outcomes than those with mean CTC count < 5 (P <  0.001). Conclusion The preoperative CTC counts in the peripheral blood of patients with HCC are closely correlated with MVI. The intraoperative manipulation of the lesion by the surgeon does not increase the number of CTCs in peripheral blood. Surgical removal of the tumor decreases the number of CTCs. The persistence of CTCs at a high level (≥ 5) after surgery suggests a risk of early recurrence. Clinical trial registration Registration number is ChiCTR-OOC-16010183, date of registration is 2016-12-18.

Six polyynes OH-1~6, some of which are occur naturally in acetylated form, had been isolated and identified from the root bark of Oplopanax horridus (Devil's Club), a natural dietary supplement and medicinal plant in North America. During the evaluation of the polyynes' potential anticancer activities, sixteen more acetylated derivatives OHR-1~16 have synthesized and their anti-proliferation activity on MCF-7, MDA-MB-231, A549, HepG2 and LO2 cells assayed to elucidate their structure-activity relationships. The results showed that OH-1 ((3S, 8S)-falcarindiol) had the most potent anticancer activity, with IC50 values of 15.3, 23.5, 7.7 and 4.7 μM on MCF-7, A549, HepG2 and MDA-MB-231 cells, respectively. For the primary structure-activity relationship, the anticancer activities of polyynes become weaker if their hydroxyl groups are acetylated, the terminal double bonds transformed into single bonds or they contain one more methylene group in the main skeleton chain.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including the Notch1 pathway in HCC. In this study, we found that Notch1 was highly expressed in HCC, especially in large HCCs. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 cells than that in HepG2 cells. HBx activated the Notch1 pathway in HepG2.2.15 cells. Suppression of HBx and the Notch1 pathway attenuated the growth of HepG2.2.15 cells. Notch1, ERK, and AKT pathways were inhibited after γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were upregulated after γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 suppressed the promoters of DUSP1 and PTEN genes, which was reversed by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we found a link among HBx, the Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC treatment.