YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells

Fos-related antigen 1(Fra-1)is a nuclear transcription factor that regulates cell growth,differentiation,and apoptosis.It is involved in the proliferation,invasion,apoptosis and epithelial mesenchymal transformation of malignant tumor cells.Fra-1 is highly expressed in gastric cancer(GC),affects the cycle distribution and apoptosis of GC cells,and participates in GC occurrence and development.However,the detailed mechanism of Fra-1 in GC is unclear,such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis.In this study,we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta(YWHAH)as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry.Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression,and affected GC cell proliferation.Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1(HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway in GC cells.Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation.These results will help to discover new molecular targets for the early diagnosis,treatment,and prognosis prediction of GC.

Differential protein expression between EBV-positive and negative epithelial cells

Epstein Barr virus infection is believed to play a role in the development of nasopharyngeal carcinoma. In order to investigate the function of EBV in epithelial cell, proteomic methods were used to find and identify the differential proteins and expected to elucidate the mechanism of EBV. Altered protein expressions were found between 293 cell (HEK293) and EBV infected cell (293-EBV). In this study, we separated differential expressed proteins using 2D-DIGE method while matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry (MALDI-TOF-MS) method was used to identify proteins. The results showed that 14 proteins were up regulated and 3 proteins were down regulated in 293-EBV cells. Bioinformatic analysis showed that these proteins are involved in cell proliferation, metastasis, apoptosis, metabolism, and signal transduction. Western blotting analysis was further carried out to verify the MS results. Thus, EBV may exert its functions by mediating differential expression of these proteins.

Role of adhesion molecules in cancer and targeted therapy

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them.Various mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor microenvironment.Recent studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell self-renewal.In this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion molecules.These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

Analysis of status and countermeasures of cancer incidence and mortality in China

Cancer is the leading cause of human deaths in the world and produces serious economic burdens. On September 12, 2018, the academic journal A Cancer Journal for Clinicians published an article about the latest statistics of cancers worldwide, which provided a status report on the global burden of 36 cancers in 185 countries worldwide. Cancer has also become a serious public health problem in China and caused more and more attention of the government and people in recent years. This review analyzes the incidence, mortality and prevalent trend of cancers in China, discusses the reasons behind this status, and reviews the potential countermeasures for cancer prevention and control in China.

A novel nonviral nanoparticle gene vector: Poly-L-lysine- silica nanoparticles

DNA delivery is a core technology for gene structure and function research as well as clinical settings. The ability to safely and efficiently targeted transfer foreign DNA into cells is a fundamental goal in biotechnology. With the development of nanobiotechnology, nanoparticle gene vectors brought about new hope to reach the goal. In our research, silica nanoparticles (SiNP) were synthesized first in a microemulsion system polyoxyethylene nonylphenyl ether (OP-10)/cyclohexane/ammonium hydroxide, at the same time the effects of SiNP size and its distribution were elucidated by orthogonal analysis; then poly-L-lysine (PLL) was linked on the surface of SiNP by nanoparticle surface energy and electrostatically binding; lastly a novel complex nanomate-rial-poly-L-lysine-silica nanoparticles (PLL-SiNP) wasprepared. The analysis of plasmid DNA binding and DNase I enzymatic degradation discovered that PLL-SiNP could bind DNA, and protect it against enzymatic degradation. Cell transfection showed that

Trend analysis of cancer incidence and mortality in China

The National Central Cancer Registry of China （NCCRC） up- dated their nationwide statistics of cancer incidence and mor- tality in China according to 2013 population-based cancer registration data （due to the time required for data collection, quality control and analysis, the latest cancer statistics avail- able in China have a 3-year lag behind the current year）.

Emerging role of metabolic reprogramming in tumor immune evasion and immunotherapy

Mounting evidence has revealed that the therapeutic efficacy of immunotherapies is restricted to a small portion of cancer patients.A deeper understanding of how metabolic reprogramming in the tumor microenvironment(TME)regulates immunity remains a major challenge to tumor eradication.It has been suggested that metabolic reprogramming in the TME may affect metabolism in immune cells and subsequently suppress immune function.Tumor cells compete with infiltrating immune cells for nutrients and metabolites.Notably,the immunosuppressive TME is characterized by catabolic and anabolic processes that are critical for immune cell function,and elevated inhibitory signals may favor cancer immune evasion.The major energy sources that supply different immune cell subtypes also undergo reprogramming.We herein summarize the metabolic remodeling in tumor cells and different immune cell subtypes and the latest advances underlying the use of metabolic checkpoints in antitumor immunotherapies.In this context,targeting both tumor and immune cell metabolic reprogramming may enhance therapeutic efficacy.

Circular RNA circCCNB1 inhibits the migration and invasion of nasopharyngeal carcinoma through binding and stabilizing TJP1 mRNA

Nasopharyngeal carcinoma(NPC)is a malignant tumor that usually occurs in people from Southeast Asia and Southern China.NPC is prone to migration and invasion,leading to poor prognosis.A large number of circular RNAs(circ RNAs)exacerbate the process of metastasis in NPC;however,their underlying mechanisms remain unclear.We found that the circular RNA circ CCNB1,encoded by the oncogene CCNB1,was downregulated in NPC biopsies and cell lines.In vitro assays show that circ CCNB1 inhibits NPC cell migration and invasion.Moreover,circ CCNB1 induces a protein,nuclear factor 90(NF90),to bind and prolong the half-life of tight junction protein 1(TJP1)m RNA.Upregulation of TJP1 enhances tight junctions between cancer cells and inhibits NPC cell migration and invasion.This study reveals a novel biological function of circ CCNB1 in the migration and invasion of NPC by enhancing the tight junctions of cancer cells by binding to NF90 proteins and TJP1 m RNA,and may provide a potential therapeutic target for NPC.

BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway

Increasing evidence has shown a strong association between tumor-suppressor genes and inflammation.However,the role of BRD7 as a novel tumor suppressor in inflammation remains unknown.In this study,by observing BRD7 knockout mice for 6–12 months,we discovered that compared with BRD7+/+mice,BRD7^(−/−)mice were more prone to inflammation,such as external inflammation and abdominal abscess.By using mouse embryo fibroblast(MEF)cells from the BRD7 knockout mouse,an in vitro lipopolysaccharide(LPS)-stimulated MEF cell line was established.The mRNA levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),chemokine(C-X-C motif)ligand 1(CXCL-1)and inducible nitric oxide synthase(iNOS)were significantly increased in BRD7^(−/−)MEF cells compared with BRD7+/+MEF cells after LPS stimulation for 1 or 6 h.In addition,the cytoplasm-to-nucleus translocation of nuclear factor kappa-B(NF-κB;p65)and an increased NF-κB reporter activity were observed in BRD7^(−/−)MEF cells at the 1 h time point but not at the 6 h time point.Furthermore,an in vivo dextran sodium sulfate(DSS)-induced acute colitis model was created.As expected,the disease activity index(DAI)value was significantly increased in the BRD7^(−/−)mice after DSS treatment for 1–5 days,which was demonstrated by the presence of a significantly shorter colon,splenomegaly and tissue damage.Moreover,higher expression levels of IL-6,TNF-α,p65,CXCL-1 and iNOS,and an increased level of NF-κB(p65)nuclear translocation were also found in the DSS-treated BRD7^(−/−)mice.These findings suggest that BRD7 has an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway,which provides evidence to aid in understanding the therapeutic effects of BRD7 on inflammatory diseases.

Overview and countermeasures of cancer burden in China

Cancer is one of the leading causes of human death worldwide.Treatment of cancer exhausts significant medical resources,and the morbidity and mortality caused by cancer is a huge social burden.Cancer has therefore become a serious economic and social problem shared globally.As an increasingly prevalent disease in China,cancer is a huge challenge for the country’s healthcare system.Based on recent data published in the Journal of the National Cancer Center on cancer incidence and mortality in China in 2016,we analyzed the current trends in cancer incidence and changes in cancer mortality and survival rate in China.And also,we examined several key risk factors for cancer pathogenesis and discussed potential countermeasures for cancer prevention and treatment in China.

AFAP1-AS1: a rising star among oncogenic long non-coding RNAs

Long non-coding RNAs(lncRNAs)have become a hotspot in biomedical research.This interest reflects their extensive involvement in the regulation of the expression of other genes,and their influence on the occurrence and development of a variety of human diseases.Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1)is a recently discovered oncogenic lncRNA.It is highly expressed in a variety of solid tumors,and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs,or by the direct binding to other proteins.Ultimately,AFAP1-AS1 promotes proliferation,chemotherapy resistance,and resistance to apoptosis,maintains stemness,and enhances invasion and migration of tumor cells.This paper summarizes the research concerning AFAP1-AS1 in malignant tumors,including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors.We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research.AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.

Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc

Actin filament associated protein 1 antisense RNA 1(named AFAP1-AS1)is a long non-coding RNA and overexpressed in many cancers.This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer.The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization.The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells.To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer,we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses.AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients'poor prognosis.In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis.AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1(named SNIP1),which inhibited ubiquitination and degradation of c-Myc protein.Upregulation of c-Myc molecule in turn promoted the expression of ZEB1,ZEB2,and SNAIL gene,which ultimately enhanced epithelial to mesenchymal transition(EMT)and lung cancer metastasis.Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer's migration and invasion may provide novel therapeutic targets for lung cancer patients'early diagnosis and therapy.

An update: Epstein-Barr virus and immune evasion via microRNA regulation

Epstein-Barr virus(EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans. To ensure its survival and maintain its B cell transformation function, EBV has developed powerful strategies to evade host immune responses. Emerging evidence has shown that micro RNAs(mi RNAs) are powerful regulators of the maintenance of cellular homeostasis. In this review, we summarize current progress on how EBV utilizes mi RNAs for immune evasion. EBV encodes mi RNAs targeting both viral and host genes involved in the immune response. The mi RNAs are found in two gene clusters, and recent studies have demonstrated that lack of these clusters increases the CD4^+ and CD8^+ T cell response of infected cells. These reports strongly indicate that EBV mi RNAs are critical for immune evasion. In addition, EBV is able to dysregulate the expression of a variety of host mi RNAs, which influence multiple immune-related molecules and signaling pathways. The transport via exosomes of EBV-regulated mi RNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment.During EBV immune evasion, viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and pro-apoptosis molecules are involved. Our increasing knowledge of the role of mi RNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.