No abstract

BackgroundCancer cells often exhibit large‐scale genomic variations, such as circular extrachromosomal DNA (ecDNA) and structural variants (SVs), which have been highly correlated with the initiation and progression of cancer. Currently, no adequate method exists to unveil how these variations regulate gene expression in heterogeneous cancer cell populations at a single‐cell resolution.MethodsHere, we developed a single‐cell multi‐omics sequencing method, scGTP‐seq, to analyse ecDNA and SVs using long‐read sequencing technologies.Results and ConclusionsWe demonstrated that our method can efficiently detect ecDNA and SVs and illustrated how these variations affect transcriptomic changes in various cell lines. Finally, we applied and validated this method in a clinical sample of hepatocellular carcinoma (HCC), demonstrating a feasible way to monitor the evolution of ecDNA and SVs during cancer progression.

Background and Aims: Liver diseases present a wide range of fibrosis, from fatty liver with no inflammation to steatohepatitis with varying degrees of fibrosis, to established cirrhosis leading to HCC. In a multivariate analysis, serum levels of spermidine were chosen as the top metabolite from 237 metabolites and its levels were drastically reduced along with progression to advanced steatohepatitis. Our previous studies that showed spermidine supplementation helps mice prevent liver fibrosis through MAP1S have prompted us to explore the possibility that spermidine can alleviate or cure already developed liver fibrosis. Methods:We collected tissue samples from patients with liver fibrosis to measure the levels of MAP1S. We treated wild-type and MAP1S knockout mice with CCl 4 -induced liver fibrosis with spermidine and isolated HSCs in culture to test the effects of spermidine on HSC activation and liver fibrosis.Results: Patients with increasing degrees of liver fibrosis had reduced levels of MAP1S. Supplementing spermidine in mice that had already developed liver fibrosis after 1 month of CCl 4 induction for an additional 3 months resulted in significant reductions in levels of ECM proteins and a remarkable improvement in liver fibrosis through MAP1S. Spermidine also suppressed HSC activation by reducing ECM proteins at both the mRNA and protein levels, and increasing the number of lipid droplets in stellate cells.

Long non-coding RNAs (lncRNAs) are involved in the gene expression regulation and usually play important roles in various human cancers, including the renal cell carcinoma (RCC). Dysregulation of certain lncRNAs are associated with the prognosis of patients with RCC. In the present review, several recently studied lncRNAs were discussed and their critical roles in proliferation, migration, invasion, apoptosis and drug resistance of renal cancer cells were revealed. The research on lncRNAs further increases our understanding on the development and progression of RCC. It is suggested that lncRNAs can be used as biomarkers or therapeutic targets for diagnosis or treatment of renal cancer. Contents1. Introduction 2. Features and functions of lncRNAs in carcinogenesis 3. lncRNAs and RCC 4. Conclusions