Baoxia He

Background: Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy characterized by extensive genetic abnormalities that might affect the prognosis and provide potential drug targets for treatment. Reprogramming of lipid metabolism plays important roles in tumorigenesis and progression and has been newly recognized a new hallmark of malignancy, and some related molecules in the signal pathways could be prognostic biomarkers and potential therapeutic targets for cancer treatment. However, the clinical value of lipid metabolism reprogramming in AML has not been systematically explored. In this study, we aim to explore the clinical value of lipid metabolism reprogramming and develop a prognostic risk signature for AML.Methods: We implemented univariate Cox regression analysis to identify the prognosis-related lipid metabolism genes, and then performed LASSO analysis to develop the risk signature with six lipid metabolism-related genes (LDLRAP1, PNPLA6, DGKA, PLA2G4A, CBR1, and EBP). The risk scores of samples were calculated and divided into low- and high-risk groups by the median risk score.Results: Survival analysis showed the high-risk group hold the significantly poorer outcomes than the low-risk group. The signature was validated in the GEO datasets and displayed a robust prognostic value in the stratification analysis. Multivariate analysis revealed the signature was an independent prognostic factor for AML patients and could serve as a potential prognostic biomarker in clinical evaluation. Furthermore, the risk signature was also found to be closely related to immune landscape and immunotherapy response in AML.Conclusions: Overall, we conducted a comprehensive analysis of lipid metabolism in AML and constructed a risk signature with six genes related to lipid metabolism for the malignancy, prognosis, and immune landscape of AML, and our study might contribute to better understanding in the use of metabolites and metabolic pathways as the potential prognostic biomarkers and therapeutic targets for AML.

Chaetoglobosins belonging to cytochalasan alkaloids represent a large class of fungal secondary metabolites. To date, around 100 chaetoglobosins and their analogues have been isolated and identified over the years from a variety of fungi, mainly from the fungus Chaetomium globosum. Studies have found that chaetoglobosins possess a broad range of biological activities, including antitumor, antifungal, phytotoxic, fibrinolytic, antibacterial, nematicidal, anti‐inflammatory, and anti‐HIV activities. This review will comprehensively summarize the biological activities and mechanisms of action of nature‐derived chaetoglobosins.

Background: The application of the oral targeted therapeutic agent sorafenib provides new hope for patients suffering from advanced stages of hepatocellular carcinoma (HCC), but the prognosis of such patients remains poor due to the rapid development of the multidrug resistance process in cancer pathogenesis. The present work evaluated whether copine-III, a novel cancer regulator encoded by the CPNE3 gene, would be a potential indicator of sorafenib resistance in HCC treatment. Materials and methods: The endogenous expression of copine-III in clinical specimens was examined by quantitative polymerase chain reaction. Copine-III siRNA was transfected into HCC cells to downregulate copine-III expression. The effect of copine-III on sorafenib’s antitumor activation was identified by in vitro and in vivo experiments (MTT, Transwell, and flow cytometry as well as a nude mice model). Results: High levels of copine-III in clinical specimens are related to poor prognosis of advanced HCC patients on sorafenib treatment. Infection of Ad-siCPNE3 significantly decreased the endogenous expression of copine-III and enhanced the susceptibility of MHCC97-H cells to sorafenib: the IC₅₀ value decreased from 1.15±0.11 to 0.25±0.05 μmol/L. Moreover, silencing copine-III enhanced the effect of sorafenib on apoptosis, in vitro invasion/migration, and subcutaneous or intrahepatic growth of MHCC97-H cells in nude mice. Conclusion: Copine-III is a novel potential indicator of prognosis for patients who received sorafenib for advanced HCC treatment.

This retrospective study was performed to evaluate the association between the UGT2B7 tagSNPs (rs12233719, rs4356975, rs7435335 and rs7441774) and breast cancer in Chinese females. Blood samples were collected from 672 patients with breast cancer and 670 healthy controls for DNA extraction. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to analyze UGT2B7 polymorphisms. Dual-luciferase reporter assays were further performed to investigate the regulatory function of UGT2B7 tagSNPs. The frequency of rs7441774 G allele in the breast cancer cases was statistically significantly higher than in the controls (0.412 vs 0.358, P = .006; odds ratio [OR] = 1.27, 95% CI = 1.08-1.48). After adjusting for conventional risk factors, individuals with the GG genotype had a higher breast cancer risk than those with the AA genotype (adjusted OR = 1.63, 95% CI = 1.18-2.26; P = .008). The GCGG haplotype of UGT2B7 was also associated with breast cancer (OR = 1.22, 95% CI = 1.04-1.45; P = .027). Meanwhile, the rs7441774 G allele could significantly decrease the transcriptional activity of the UGT2B7 gene. This study indicates that UGT2B7 polymorphisms may play a crucial role in the occurrence and development of breast cancer in the Han Chinese population.

MicroRNA-542-3p inhibits oral squamous cell carcinoma progression by inhibiting ILK/TGF-1/Smad2/3 signaling MicroRNA-542-3p inhibits oral squamous cell carcinoma progression by inhibiting ILK/TGF-β1/Smad2/3 signaling

The aim of our study was to investigate the effects of miR‐133a‐3p on human oral squamous cell carcinoma (OSCC) cells by regulating gene COL1A1. OSCC tissues, adjacent tongue epithelial tissues, the immortalized oral epithelial cell line HIOEC, and OSCC cell lines (CAL‐27, TCA‐8113, SCC‐4, SCC‐9, and SCC‐15) were used in this research. Quantitative real‐time PCR (RT‐qPCR) was employed to determine the expression of miR‐133a‐3p and COL1A1. Dual luciferase reporter gene assay and Western blot were applied to verify the binding relationship between miR‐133a‐3p and COL1A1. Functional assays were also conducted in this study, including CCK‐8 assay, colony formation assay, flow cytometry analysis as well as Transwell assay. MiR‐133a‐3p was found low‐expressed both in OSCC tissues and cells lines compared with normal tissues and cell line, respectively, whereas COL1A1 was just the opposite. The over‐expression of miR‐133a‐3p or the down‐regulation of COL1A1 suppressed the proliferation, invasion, and mitosis of OSCC cells, whereas simultaneous down‐regulation of miR‐133a‐3p and up‐regulation of COL1A1 led to no significant alteration of cell activities. MiR‐133a‐3p could inhibit the proliferation and migration of OSCC cells through directly targeting COL1A1 and reducing its expression. J. Cell. Biochem. 119: 338–346, 2018.