Hepatocellular carcinoma (HCC) is one of the most common solid malignancies in the world. Due to the limited effectiveness of current drug treatments, further research on HCC is necessary. PANoptosis is defined as an inflammatory RCD whose main features combine pyroptosis, apoptosis and necroptosis which cannot be explained by any of these three RCDs alone. In HCC, risk stratification based on PANoptosis-associated lncRNAs has clinical application potential. In this study, we explored HCC related PANoptosis-related lncRNAs (PRLs) by analyzing significantly differentially expressed genes in HCC. HCC-associated PRL scores were established by WGCNA, LASSO analysis and multivariate Cox assessment. Subsequently, we verified the prognostic analysis ability of PRL score for HCC patients, and on this basis established a prognostic risk assessment model for HCC and verified its reliability. The relationship between PRL score and immune infiltration as well as drug sensitivity was further analyzed to evaluate the clinical reference value of this model. Western blot analysis and PCR further verified the reliability of bioinformatics results. The observed suppression of HCC progression and invasiveness following selected PRL knockdown further validated the reliability of our bioinformatics analysis results. Our results provide new evidence for the role of PANoptosis-associated lncRNAs in HCC.

Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) are promising targets or agents for the treatment of human cancers. Most liver-specific lncRNAs exhibit loss of expression and act as tumor suppressors in liver cancer. Modulating the expression of these liver-specific lncRNAs is a potential approach for lncRNA-based gene therapy for hepatocellular carcinoma (HCC). Here, we report that the expression of the liver-specific lncRNA FAM99B is significantly decreased in HCC tissues and that FAM99B suppresses HCC cell proliferation and metastasis both in vitro and in vivo. FAM99B promotes the nuclear export of DDX21 through XPO1, leading to further cleavage of DDX21 by caspase3/6 in the cytoplasm. FAM99B inhibits ribosome biogenesis by inhibiting ribosomal RNA (rRNA) processing and RPS29/RPL38 transcription, thereby reducing global protein synthesis through downregulation of DDX21 in HCC cells. Interestingly, the FAM99B65-146 truncation exhibits tumor-suppressive effects in vivo and in vitro. Moreover, GalNAc-conjugated FAM99B65-146 inhibits the growth and metastasis of orthotopic HCC xenografts, providing a new strategy for the treatment of HCC. This is the first report of the use of a lncRNA as an agent rather than a target in tumor treatment. Graphical illustration of the mechanism of FAM99B in HCC.

Hepatocellular carcinoma (HCC) represents a major malignancy globally, characterized by high malignancy and intricate molecular mechanisms. This study aims to explore the role of the long non-coding RNA (lncRNA) lnc-EST885 in HCC development.

Cell experiments including FISH, western blot, flow cytometry and functional analysis were used to elucidate the effects of lnc-EST885 on cell proliferation, apoptosis, migration and EMT processes. RNA pull-down and ESI-FT-ICR-MS were used to identify proteins that interact with lnc-EST885 and were verified by RIP-qPCR. Furthermore, the association of lnc-EST885 and TRAF4 with HCC prognosis and metastasis was evaluated through bioinformatics analysis and animal models.

lnc-EST885 is one of the lncRNAs with the highest expression levels in M2-type macrophages. The expression of lnc-EST885 in HCC tissues is significantly higher than in normal tissues, and high expression is associated with poor prognosis. Functional experiments have shown that lnc-EST885 significantly promotes the proliferation and migration of liver cancer cells, inhibits apoptosis, and induces EMT. Studies in a mouse lung metastasis model have also confirmed that lnc-EST885 promotes the pulmonary metastasis of HCC cells in vivo. Mechanistic studies have revealed that lnc-EST885 can bind to the TRAF4 protein, activating the PI3K/AKT signaling pathway, thereby promoting the proliferation, migration, and EMT capability of liver cancer cells, contributing to the malignant phenotype of HCC.

lnc-EST885 plays a crucial role in the development of liver cancer, serving as a potential biomarker for predicting HCC prognosis and providing a new target for HCC treatment.

Hepatitis C virus (HCV) is a hepatotropic virus that can be transmitted through unsafe medical procedures, such as injections, transfusions, and dental treatment. The infection may be self-limiting or manifest as a chronic form that induces liver fibrosis, cirrhosis, or progression into hepatocellular carcinoma (HCC). Epigenetic mechanisms are major regulators of gene expression. These mechanisms involve DNA methylation, histone modifications, and the activity of non-coding RNAs, which can enhance or suppress gene expression. Abnormal activity or the dysregulated expression of epigenetic molecules plays an important role in the pathogenesis of various pathological disorders, including inflammatory diseases and malignancies. In this review, we summarise the current evidence on epigenetic mechanisms involved in HCV infection and progression to HCC.

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, with high morbidity and occurrence. Although various therapeutic approaches have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of HCC remain enigmatic. The N6-methyladenosine (m6A) RNA modification is believed to regulate RNA metabolism and further gene expression. This process is intricately regulated by multiple regulators, such as methylases and demethylases. Non-coding RNAs (ncRNAs) are involved in the regulation of the epigenetic modification, mRNA transcription and other biological processes, exhibiting crucial roles in tumor occurrence and development. The m6A-ncRNA interaction has been implicated in the malignant phenotypes of HCC and plays an important role in drug resistance. This review summarizes the effect of m6A-ncRNA crosstalk on HCC progression and their clinical implications as prognostic markers and therapeutic targets in this disease.

DNA damage repair (DDR) may affect tumorigenesis and therapeutic response in hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) can regulate DDR and play a vital role in maintaining genomic stability in cancers. Here, we identified a DDR-related prognostic signature in HCC and explored its potential clinical value.

Data of HCC samples were obtained from the Cancer Genome Atlas (TCGA), and a list of DDR-related genes was extracted from the Molecular Signatures database (MSigDB). A DDR-related lncRNAs signature associated to overall survival (OS) was constructed using the least absolute shrinkage and selection operator-cox regression, and was further validated by the Kaplan-Meier curve and receiver operating characteristic curve. A nomogram integrating other clinical risk factors was established. Moreover, the relationships between the signature with somatic mutation, immune landscape and drug sensitivity were explored.

The prognostic model of 5 DDR-related lncRNAs was constructed and classified patients into two risk groups at median cut-off. The low-risk group had a better OS, and the signature was an independent prognostic indicator in HCC. A nomogram of the signature combined with TNM stage was constructed. TP53 gene was more frequently mutated in the high-risk group. Marked differences in immune cells were observed, such as CD4 + T cells, NK cells and macrophages, between the two groups. Moreover, an increase in the expression of immune checkpoint molecules was found in the high-risk group. The low-risk group presented with a significantly higher response to sorafenib or cisplatin. Finally, potential value of this signature was validated in real-world HCC patients.

Our findings provided a promising insight into DDR-related lncRNAs in HCC and a personalized prediction tool for prognosis and therapeutic response.

Infantile hemangiomas (IHs) are commonly observed benign tumors that can cause serious complications. M2-polarized macrophages in IHs promote disease progression. In this study, we investigated the role of M2 macrophage-derived exosomal lncRNA MIR4435-2HG in IHs.

Exosomes derived from M2 polarized macrophages were extracted. Next, using cell co-culture or transfection, we investigated whether M2 polarized macrophage-derived exosomes (M2-exos) can transport MIR4435-2HG to regulate the proliferation, migration, invasion, and angiogenesis of hemangioma-derived endothelial cells (HemECs). RNA-seq and RNA pull-down assays were performed to identify targets and regulatory pathways of MIR4435-2HG. We explored the possible mechanisms through which MIR4435-2HG regulates the biological function of HemECs.

M2-exos significantly enhanced the proliferation, migration, invasion, and angiogenesis of HemECs. Thus, HemECs uptake M2-exos and promote biological functions through the inclusion of MIR4435-2HG. RNA-seq and RNA pull-down experiments confirmed that MIR4435-2HG regulates of HNRNPA1 expression and directly binds to HNRNPA1, consequently affecting the NF-κB signal pathway.

MIR4435-2HG of M2-exos promotes the progression of IHs and enhances the proliferation, migration, invasion, and angiogenesis of HemECs by directly binding to HNRNPA1. This study not only reveals the mechanism of interaction between M2 macrophages and HemECs, but also provides a promising therapeutic target for IHs.