AIMTo determine whether circular RNAs (circRNAs) are involved in pathological processes of gastric cancer (GC).METHODSThree circRNAs with differential expression in GC and colorectal cancer were randomly selected for validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using 20 pairs of gastric tissues and normal tissues. Based on the predicted circRNA-miRNA network, we then focused on hsa_circ_0000745, which was found to be down-regulated in 20 GC tissues compared with normal tissues. The hsa_circ_0000745 levels were further analyzed by qRT-PCR in 60 GC tissues and paired adjacent non-tumor tissues, as well as 60 plasma samples from GC patients and 60 plasma samples from healthy controls. The associations between the levels of hsa_circ_0000745 and the clinicopathological features of GC patients were statistically assessed. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0000745 in GC.RESULTSHsa_circ_0000745 was down-regulated in GC tissues vs non-tumorous tissues (P < 0.001) and in plasma samples from patients with GC vs healthy controls (P < 0.001). The expression level of hsa_circ_0000745 in GC tissues correlated with tumor differentiation, while the expression level in plasma correlated with tumor-node-metastasis stage. The area under the ROC curve (AUC) of hsa_circ_0000745 in plasma was 0.683, suggesting good diagnostic value. Plasma hsa_circ_0000745 level combined with carcinoembryogenic antigen (CEA) level increased the AUC to 0.775.CONCLUSIONHsa_circ_0000745 plays an important role in GC and its expression level in plasma in combination with CEA level is a promising diagnostic marker for this malignancy.

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Background: There is increasing evidence that circular RNAs (circRNAs) play an important role in human cancers. As a newly identified human circular RNA, circ_0006282 is abnormally expressed in several types of cancers and promotes the development of cancers. However, the expression and function of circ_0006282 in gastric cancer (GC) remain unclear. Methods: The expression of circ_0006282 in cancer tissues and adjacent non-cancer tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR) method, and the relationship between circ_0006282 expression and clinicopathological parameters was analyzed. After knockdown of circ_0006282 by RNA interference in GC cells, CCK-8 assay, colony formation and transwell assays were conducted to examine the effects of circ_0006282 on GC cells. The influence of circ_0006282 on tumor growth in vivo was assessed in a xenograft model. Furthermore, regulatory relationship between circ_0006282, miR-155 and FBXO22 was detected by luciferase assay, qRT-PCR and Western blot. Results: The expression of circ_0006282 in GC tissues was significantly higher than its adjacent non-cancer tissues and over-expression of circ_0006282 was associated with tumor size, lymph nodes metastasis and TNM stage, but no obvious links with other pathological parameters. Knockdown of circ_0006282 inhibited the proliferation and metastasis ability of GC cells in vitro and suppressed the tumor growth in vivo. Furthermore, mechanistic investigations suggested that circ_0006282 served as a competing endogenous RNA (ceRNA) of miR-155. Moreover, FBXO22 was identified as the functional target of miR-155 and down-expression of circ_0006282 inhibited FBXO22 expression. Rescue assays also demonstrated that the oncogenic function of circ_0006282 is partly attributed to its regulation on miR-155/FBXO22 axis. Conclusion: Our findings indicated that over-expression of circ_0006282 down-regulated miR-155 to activate the expression of FBXO22, thus promoting proliferation and metastasis of GC cells, which provides a promising therapeutic target for GC treatment.

A phytochemical investigation of the branches and leaves of Cephalotaxus lanceolata resulted in the isolation of three new cephalotaxus alkaloids, cephalancetines A, B, and D (1, 2, and 4, resp.), together with ten known alkaloids, 3 and 5-13. The structures of the alkaloids were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR, and HR-ESI-MS, and single-crystal X-ray diffraction. All isolated compounds were tested for their cytotoxicities against four human tumor cell lines, A549, HCT116, SK-BR-3, and HepG2. Compounds 12 and 13 showed remarkable activities against A549, HCT116, and HepG2 cell lines.

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Three structurally related 6-C-methyl flavonoids isolated from Pinus densata, including 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (PD1), 5,7,4'-trihydroxy-3,8-dimethoxy-6-C-methylflavone (PD2), and 5,7,4'-trihydroxy-3-methoxy-6-C-methylflavone (PD3), were tested for their ability to inhibit the proliferation and promote the apoptosis of the HL-60 human leukaemia cell line. Cytotoxicity assays in the HL-60 human cancer cell line demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone exhibited the most potent cytotoxicity of the three structurally related 6-C-methyl flavonoids. 5,4'-Dihydroxy-3,7,8-trimethoxy-6-C-methylflavone inhibited the proliferation of HL-60 cells in a dose-dependent manner with an IC₅₀ of 7.91 µM (48 h treatment). Furthermore, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-induced apoptosis was associated with mitochondrial membrane disruption and cytochome c release. Flow cytometry analyses revealed an increase in the hypodiploid population in 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-treated HL-60 cells. Treatment with a concentration of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone that induced apoptosis activated caspase-3 but did not activate caspase-1. A caspase-3 inhibitor (Ac-DEVD-CHO), but not a caspase-1 inhibitor (Ac-YVAD-CHO), reversed the cytotoxic effects of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone in HL-60 cells. These data demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone effectively induced the apoptosis of HL-60 cells and exhibited significant anticancer activity via the mitochondrial caspase-3-dependent apoptosis pathway.

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Seven new diterpenoids lanceolatins A-G (1-7), together with five known diterpenoids (8-12), were isolated from the branches and leaves of Cephalotaxus lanceolata. The structures of the new diterpenoids were elucidated based on spectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS. Single crystal X-ray diffraction (CuK α radiation) was employed to confirm the structure of lanceolatin G (7), and finally 10 established its absolute configuration. Compound 12 showed significant inhibition against human tumor cell lines HCT116 and HepG2 with IC 50 values of 0.17 and 0.63 µg/mL, respectively, while compounds 3-5 can inhibit nitric oxide (NO) release in LPS-induced RAW264.7 macrophages with IC 50 values of 8.72, 10.79, 12.73 µM.