Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma

BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell functions.At present,the application of B56εin pan-cancer lacks a comprehensive analysis,and its role and mechanism in hepatocellular carcinoma(HCC)are still unclear.The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Profiling Interactive Analysis,and Tumor Immune Estimation Resource databases were used to analyze B56εexpression,prognostic mutations,somatic copy number alterations,and tumor immune characteristics in 33 tumors.The relationships between B56εexpression levels and drug sensitivity,immuno-therapy,immune checkpoints,and human leukocyte antigen(HLA)-related genes were further analyzed.Gene Set Enrichment Analysis(GSEA)was performed to reveal the role of B56εin HCC.The Cell Counting Kit-8,plate cloning,wound healing,and transwell assays were conducted to assess the effects of B56εinterference on the malignant behavior of HCC cells.RESULTS In most tumors,B56εexpression was upregulated,and high B56εexpression was a risk factor for adrenocortical cancer,HCC,pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma(all P<0.05).B56εexpression levels were correlated with a variety of immune cells,such as T helper 17 cells,B cells,and macro-phages.There was a positive correlation between B56εexpression levels with immune checkpoint genes and HLA-related genes(all P<0.05).The expression of B56εwas negatively correlated with the sensitivity of most chemotherapy drugs,but a small number showed a positive correlation(all P<0.05).GSEA analysis showed that B56εexpression was related to the cancer pathway,p53 downstream pathway,and interleukin-mediated signaling in HCC.Knockdown of B56εexpression in HCC cells inhibited the proliferation,migration,and invasion capacity of tumor cells.Core Tip:The expression of protein phosphatase 2A(PP2A)subunit B56εis up-regulated in most tumors,and its high expression is a risk factor for adrenocortical cancer,hepatocellular carcinoma(HCC),pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma.B56εexpression levels correlate with immune cells,immune checkpoint genes,human leukocyte antigen-related genes,and the sensitivity of chemotherapy drugs.In HCC,B56εexpression is related to the cancer pathway.Knockdown of B56εexpression in HCC cells can inhibit the proliferation,migration and invasion capacity of tumor cells.Our study supports PP2A subunit B56εas a prognostic marker and potential therapeutic target for HCC.

Potential and application of abortive transcripts as a novel molecular marker of cancers

Abortive transcript(AT)is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage.Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments.Therefore,the distribution of AT length and the scale of abortive initiation are correlated to the promoter,discriminator,and transcription initiation sequence,and can be affected by transcription elongation factors.AT plays an important role in the occurrence and development of various diseases.Here we summarize the discovery of AT,the factors responsible for AT formation,the detection methods and biological functions of AT,to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.

Dietary vitamins modified the association of dietary iron with type 2 diabetes:the National Health and Nutrition Examination Survey,2003-2014

To the Editor:The epidemic of diabetes mellitus poses a major public health threat worldwide.In the United States,the prevalence of type 2 diabetes(T2D)affected 13.9%of adults and would continually increase.[1]Diet is one of the major lifestyle risk factors for T2D,in which dietary iron has generated substantial interest over the past 20 years.[2,3]It is to be noted that dietary vitamins A,B2,B6,E,C,and folic acid were reported to affect the absorption or oxidation of iron in body.[4]However,whether these dietary vitamins play a role in iron-related T2D remains unclear.Further research revealing the holistic role of these dietary vitamins in the association between iron and T2D is needed,which would provide important guidance for decreasing the risk of iron-related T2D.The present study aimed to examine the association between dietary iron and T2D in the National Health and Nutrition Examination Survey(NHANES)and evaluate whether holistic dietary vitamins affect this relationship.

Electrochemically mediated three-component synthesis of isothioureas using thiols as sulfur source

The simultaneous binding/dissociation of multiple bonds in a one-pot manner by multicomponent reactions provide an important approach for developing novel and sustainable pathway in the drug discovery process.Herein we develop an electrocatalytic three-component reaction to construct multifunctional and valuable isothiourea compounds,which uses thiols,isocyanides and amines as substrates.Compared with the previous work,the organic electrosynthesis technique can avoid the requirement of heavy metal catalysts and stoichiometric oxidants.In addition,using thiol as a substrate to participate in the three-component reaction broadens the source of sulfur,which can also construct more abundant isothiourea derivatives.