Gene expression profiling of MYC-driven tumor signatures in porcine liver stem cells by transcriptome sequencing

AIM:To identify the genes induced and regulated by the MYC protein in generating tumors from liver stem cells.METHODS:In this study,we have used an immortal porcine liver stem cell line,PICM-19,to study the role of c-MYC in hepatocarcinogenesis.PICM-19 cells were converted into cancer cells(PICM-19-CSCs)by overexpressing human MYC.To identify MYC-driven differential gene expression,transcriptome sequencing was carried out by RNA sequencing,and genes identified by this method were validated using real-time PCR.In vivo tumorigenicity studies were then conducted by injecting PICM-19-CSCs into the flanks of immunodeficient mice.RESULTS:Our results showed that MYC-overexpressing PICM-19 stem cells formed tumors in immunodeficient mice demonstrating that a single oncogene was sufficient to convert them into cancer cells(PICM-19-CSCs).By using comparative bioinformatics analyses,we have determined that>1000 genes were differentially expressed between PICM-19 and PICM-19-CSCs.Gene ontology analysis further showed that the MYCinduced,altered gene expression was primarily associated with various cellular processes,such as metabolism,cell adhesion,growth and proliferation,cell cycle,inflammation and tumorigenesis.Interestingly,six genes expressed by PICM-19 cells(CDO1,C22orf39,DKK2,ENPEP,GPX6,SRPX2)were completely silenced after MYC-induction in PICM-19-CSCs,suggesting that the absence of these genes may be critical for inducingtumorigenesis.CONCLUSION:MYC-driven genes may serve as promising candidates for the development of hepatocellular carcinoma therapeutics that would not have deleterious effects on other cell types in the liver.

The pros and cons of biological effects of herbs and herb-derived compounds on liver tumorigenesis

Consumption of natural products such as herbs,spices,plant-derived compounds,and foods is on the rise globally.The use of these substances is widely recognized as an integral part of culture and tradition,with the philosophy being“no benefit is no harm”.The utility of medicinal plants and extracts is under scrutiny,and the scientific community needs to clarify many conceptual gaps.Medicinal plants are rich in bioactive phytochemicals that produce chemopreventive effects at different levels,including cellular,animal,and clinical.The ultimate translational value is often missing,and some studies suggest that botanicals may contain toxic compounds that cause acute or chronic toxicity.In this regard,the liver is the center,and herbal products can show protective effects or induce hepatotoxicity,thereby promoting liver cancer.In this review article,we examine a range of herbal products implicated in hepatocarcinogenesis and extend the discussion to herbal products that may be potentially involved in the prevention and treatment of liver carcinoma.

The mechanism of dysbiosis in alcoholic liver disease leading to liver cancer

Currently, alcoholic liver disease (ALD) is one of the most prevalent chronic liver diseases worldwide, representing one of the main etiologies of cirrhosis and hepatocellular carcinoma (HCC). Although we do not know the exact mechanisms by which only a selected group of patients with ALD progress to the final stage of HCC, the role of the gut microbiota within the progression to HCC has been intensively studied in recent years. To date, we know that alcohol-induced gut dysbiosis is an important feature of ALD with important repercussions on the severity of this disease. In essence, an increased metabolism of ethanol in the gut induced by an excessive alcohol consumption promotes gut dysfunction and bacterial overgrowth, setting a leaky gut. This causes the translocation of bacteria, endotoxins, and ethanol metabolites across the enterohepatic circulation reaching the liver, where the recognition of the pathogen-associated molecular patterns via specific Toll-like receptors of liver cells will induce the activation of the nuclear factor kappa-B pathway, which releases pro-inflammatory cytokines and chemokines. In addition, the mitogenic activity of hepatocytes will be promoted and cellular apoptosis will be inhibited, resulting in the development of HCC. In this context, it is not surprising that microbiota-regulating drugs have proven effectiveness in prolonging the overall survival of patients with HCC, making attractive the implementation of these drugs as co-adjuvant for HCC treatment.