Elevated choline drives KLF5-dominated transcriptional reprogramming to facilitate liver cancer progression.

An increase in the total choline-containing compound content is a common characteristic of cancer cells, and aberrant choline metabolism in cancer is closely associated with malignant progression. However, the potential role of choline-induced global transcriptional changes in cancer cells remains unclear. In this study, we reveal that an elevated choline content facilitates hepatocellular carcinoma (HCC) cell proliferation by reprogramming Krüppel-like factor 5 (KLF5)-dominated core transcriptional regulatory circuitry (CRC).

Heat shock transcription factor 1 facilitates liver cancer progression by driving super-enhancer-mediated transcription of MYCN.

Background: Heat shock transcription factors (HSFs) play crucial roles in the development of malignancies. However, the specific roles of HSFs in hepatocellular carcinoma (HCC) have yet to be fully elucidated.

Aims: To explore the involvement of the HSF family, particularly HSF1, in the progression and prognosis of HCC.

Fibrillarin reprograms glucose metabolism by driving the enhancer-mediated transcription of PFKFB4 in liver cancer.

DNA- and RNA-binding proteins (DRBPs) are versatile proteins capable of binding to both DNA and RNA molecules. In this study, we identified fibrillarin (FBL) as a key DRBP that is upregulated in liver cancer tissues vs. normal tissues and is correlated with patient prognosis.

LTR retrotransposon-derived LncRNA LINC01446 promotes hepatocellular carcinoma progression and angiogenesis by regulating the SRPK2/SRSF1/VEGF axis.

The causal link between long terminal repeat (LTR) retrotransposon-derived lncRNAs and hepatocellular carcinoma (HCC) remains elusive and whether these cancer-exclusive lncRNAs contribute to the effectiveness of current HCC therapies is yet to explore. Here, we investigated the activation of LTR retrotransposon-derived lncRNAs in a broad range of liver diseases. We found that LTR retrotransposon-derived lncRNAs are mainly activated in HCC and is correlated with the proliferation status of HCC.

Long-read transcriptome landscapes of primary and metastatic liver cancers at transcript resolution.

Background: The liver ranks as the sixth most prevalent site of primary cancer in humans, and it frequently experiences metastases from cancers originating in other organs. To facilitate the development of effective treatments and improve survival rates, it is crucial to comprehend the intricate and diverse transcriptome landscape of primary and metastatic liver cancers.

Methods: We conducted long-read isoform sequencing and short-read RNA sequencing using a cohort of 95 patients with primary and secondary liver cancer who underwent hepatic resection.

FLIBase: a comprehensive repository of full-length isoforms across human cancers and tissues.

Regulatory processes at the RNA transcript level play a crucial role in generating transcriptome diversity and proteome composition in human cells, impacting both physiological and pathological states. This study introduces FLIBase (www.FLIBase.

Aldolase A Accelerates Cancer Progression by Modulating mRNA Translation and Protein Biosynthesis via Noncanonical Mechanisms.

Aldolase A (ALDOA), a crucial glycolytic enzyme, is often aberrantly expressed in various types of cancer. Although ALDOA has been reported to play additional roles beyond its conventional enzymatic role, its nonmetabolic function and underlying mechanism in cancer progression remain elusive. Here, it is shown that ALDOA promotes liver cancer growth and metastasis by accelerating mRNA translation independent of its catalytic activity.

Hepatic ARID3A facilitates liver cancer malignancy by cooperating with CEP131 to regulate an embryonic stem cell-like gene signature.

Liver cancer stemness refers to the stem cell-like phenotype of hepatocarcinoma cells and is closely related to a high degree of tumour malignancy. Here, we identified AT-rich interacting domain 3A (ARID3A) as one of the most upregulated stemness-related transcription factors in liver cancer by an in vitro functional screen. ARID3A can promote liver cancer cell viability and metastasis both in vitro and in vivo.

CRISPR/Cas9 Screens Reveal that Hexokinase 2 Enhances Cancer Stemness and Tumorigenicity by Activating the ACSL4-Fatty Acid β-Oxidation Pathway.

Metabolic reprogramming is often observed in carcinogenesis, but little is known about the aberrant metabolic genes involved in the tumorigenicity and maintenance of stemness in cancer cells. Sixty-seven oncogenic metabolism-related genes in liver cancer by in vivo CRISPR/Cas9 screening are identified. Among them, acetyl-CoA carboxylase 1 (ACC1), aldolase fructose-bisphosphate A (ALDOA), fatty acid binding protein 5 (FABP5), and hexokinase 2 (HK2) are strongly associated with stem cell properties.

RNA binding protein RALY activates the cholesterol synthesis pathway through an MTA1 splicing switch in hepatocellular carcinoma.

Alternative splicing is an important RNA processing event that contributes to RNA complexity and protein diversity in cancer. Accumulating evidence demonstrates the essential roles of some alternatively spliced genes in carcinogenesis. However, the potential roles of alternatively spliced genes in hepatocellular carcinoma (HCC) are still largely unknown.

SRTdb: an omnibus for human tissue and cancer-specific RNA transcripts.

The production of functional mature RNA transcripts from genes undergoes various pre-transcriptional regulation and post-transcriptional modifications. Accumulating studies demonstrated that gene transcription carries out in tissue and cancer type-dependent ways. However, RNA transcript-level specificity analysis in large-scale transcriptomics data across different normal tissue and cancer types is lacking.

RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1.

Unlabelled: RNA helicases are dysregulated in tumors. Here, we identified DHX37 as one of the top RNA helicase genes with upregulated expression in hepatocellular carcinoma (HCC). DHX37 promoted proliferation of liver cancer cells in vitro and in vivo.

A pathway-guided strategy identifies a metabolic signature for prognosis prediction and precision therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal and heterogeneous disease with a poor prognosis and no effective treatments. Herein, we presented a pathway-guided computational framework to establish a metabolic signature with the capacity for HCC prognosis prediction. By using the TCGA dataset as a training cohort (n = 365), we built an eight-gene (ACADS, ALDH1A2, FTCD, GOT2, GPX7, HADHA, LDHA and UGT2A1) risk score called the MGP score from the 20 metabolic pathways downregulated in HCC.

Application of third-generation sequencing in cancer research.

In the past several years, nanopore sequencing technology from Oxford Nanopore Technologies (ONT) and single-molecule real-time (SMRT) sequencing technology from Pacific BioSciences (PacBio) have become available to researchers and are currently being tested for cancer research. These methods offer many advantages over most widely used high-throughput short-read sequencing approaches and allow the comprehensive analysis of transcriptomes by identifying full-length splice isoforms and several other posttranscriptional events. In addition, these platforms enable structural variation characterization at a previously unparalleled resolution and direct detection of epigenetic marks in native DNA and RNA.

HNRNPL Circularizes ARHGAP35 to Produce an Oncogenic Protein.

Circular RNAs (circRNAs) are an intriguing class of widely prevalent endogenous RNAs, the vast majority of which have not been characterized functionally. Here, we identified a novel oncogenic circRNA originating from the back-splicing of Exon2 and Exon3 of a tumor suppressor gene, ARHGAP35 (also known as P190-A), termed as circARHGAP35. have observe that circARHGAP35 and linear ARHGAP35 have antithetical expression and functions.

Optimized protocol for an inducible rat model of liver tumor with chronic hepatocellular injury, inflammation, fibrosis, and cirrhosis.

Animal models of liver cancer are instrumental in the study of hepatocarcinogenesis and development of novel therapeutic approaches. Here, we describe steps to establish liver cancer in a rat model, via chronic administration of diethylnitrosamine. This causes liver tumors with a sequential progression of hepatitis, cirrhosis, and tumor formation, which closely mimics the development of human liver cancer.

Characterization of the dual functional effects of heat shock proteins (HSPs) in cancer hallmarks to aid development of HSP inhibitors.

Background: Heat shock proteins (HSPs), a representative family of chaperone genes, play crucial roles in malignant progression and are pursued as attractive anti-cancer therapeutic targets. Despite tremendous efforts to develop anti-cancer drugs based on HSPs, no HSP inhibitors have thus far reached the milestone of FDA approval. There remains an unmet need to further understand the functional roles of HSPs in cancer.

The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model.

Hepatocellular carcinoma (HCC) initiation is characterized by stepwise accumulation of molecular alterations, during which the early events are largely unknown. Here, we presented a comprehensive genomic and transcriptomic landscape at stages of hepatitis, cirrhosis, and HCC by using a diethylnitrosamine-induced rat HCC model. We observed the early occurrence of gene instability and aberrant cancer associated signaling pathways in liver hepatitis.

Inflammation-Induced Long Intergenic Noncoding RNA (LINC00665) Increases Malignancy Through Activating the Double-Stranded RNA-Activated Protein Kinase/Nuclear Factor Kappa B Pathway in Hepatocellular Carcinoma.

Background And Aims: The nuclear factor kappa B (NF-κB) signaling pathway is important for linking inflammation and tumorigenesis. Here, we characterized an NF-κB signaling activation-induced long intergenic noncoding (LINC) RNA in hepatocellular carcinoma (HCC), LINC00665, that contributes to the enhanced cell proliferation of HCC cells both in vitro and in vivo.

Approach And Results: LINC00665 physically interacts with the double-stranded RNA (dsRNA)-activated protein kinase (PKR), enhances its activation, and maintains its protein stability by blocking ubiquitin/proteasome-dependent degradation, resulting in a positive feedback regulation of NF-κB signaling in HCC cells.

An LTR Retrotransposon-Derived Long Noncoding RNA lncMER52A Promotes Hepatocellular Carcinoma Progression by Binding p120-Catenin.

Long terminal repeat (LTR) retrotransposons are a major class of transposable elements, accounting for 8.67% of the human genome. LTRs can serve as regulatory sequences and drive transcription of tissue or cancer-specific transcripts.

Splicing Regulator p54 /Non-POU Domain-Containing Octamer-Binding Protein Enhances Carcinogenesis Through Oncogenic Isoform Switch of MYC Box-Dependent Interacting Protein 1 in Hepatocellular Carcinoma.

Background And Aims: Alternative splicing (AS) is a key step that increases the diversity and complexity of the cancer transcriptome. Recent evidence has highlighted that AS has an increasingly crucial role in cancer. Nonetheless, the mechanisms underlying AS and its dysregulation in hepatocellular carcinoma (HCC) remain elusive.

Comprehensive characterization of circular RNAs in ~ 1000 human cancer cell lines.

Background: Human cancer cell lines are fundamental models for cancer research and therapeutic strategy development. However, there is no characterization of circular RNAs (circRNAs) in a large number of cancer cell lines.

Methods: Here, we apply four circRNA identification algorithms to heuristically characterize the expression landscape of circRNAs across ~ 1000 human cancer cell lines from CCLE polyA-enriched RNA-seq data.

Tumor-Specific Transcripts Are Frequently Expressed in Hepatocellular Carcinoma With Clinical Implication and Potential Function.

Hepatocellular carcinoma (HCC) is a highly lethal cancer and its underlying etiology remains understudied. The immense diversity and complexity of the cancer transcriptome hold the potential to yield tumor-specific transcripts (TSTs). Here, we showed that hundreds of TSTs are frequently expressed in HCC by an assembling spliced junction analysis of RNA sequencing raw data from approximately 1,000 normal and HCC tissues.

Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma.

The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC, but there has been no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs.

Hepatic SMARCA4 predicts HCC recurrence and promotes tumour cell proliferation by regulating SMAD6 expression.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is typically diagnosed at advanced stages. Identification and characterisation of genes within amplified and deleted chromosomal loci can provide new insights into the pathogenesis of cancer and lead to new approaches for diagnosis and therapy. In our previous study, we found a recurrent region of copy number amplification at 19p13.