Background: Growing evidences have been revealing that long noncoding RNAs are vital factors in oncogenesis and tumor development. Among them, cancer susceptibility candidate 11 (CASC11) has displayed an impressively essential role in various kinds of cancers including hepatocellular carcinoma (HCC). Nevertheless, its role and potential mechanism in HCC still remain to be fully investigated.Methods: CASC11 expression level was evaluated by real‐time polymerase chain reaction, western blotting, and in situ hybridization staining in HCC patients, and its prognostic effect was analyzed. The role of CASC11 in HCC tumorigenesis and progression was investigated by cell proliferation assay, transwell assay, extracellular acidification rate, western blotting, flow cytometry, and an in vivo xenograft model. The interactions among CASC11, E2F transcription factor 1 (E2F1), and eukaryotic translation initiation factor 4A3 (EIF4A3) were explored by using quantitative reverse transcriptase polymerase chain reaction, western blotting, RNA‐binding protein immunoprecipitation assay, and chromatin immunoprecipitation assays.Results: Upregulation of CASC11 was confirmed in HCC tissues and associated with poor prognosis. Loss of function assays showed inhibition of CASC11 expression suppressed HCC cells proliferation, mobility, and glucose metabolism and promoted apoptosis. E2F1 expression significantly decreased after inhibition of CASC11. Rescue experiments illustrated that E2F1 overexpression alleviated the suppression of CASC11 inhibition on HCC progression in vitro and in vivo. Mechanistically, CASC11 recruited EIF4A3 to enhance the stability of E2F1 mRNA. CASC11 and E2F1 impacted the activation of the NF‐κB signaling and PI3K/AKT/mTOR pathway and further regulated the expression PD‐L1 that is an important target of immunotherapy. In addition, we identified YY1 could modulate CASC11 expression by binding to its promoter.Conclusions: Our data revealed that CASC11 promoted the progression of HCC by means of EIF4A3‐mediated E2F1 upregulation, indicating CASC11 is a promising diagnostic biomarker and therapeutic target for HCC.

Chemo-resistance prominently hampers the effects of systemic chemotherapy to cholangiocarcinoma (CCA). Long non-coding RNAs (lncRNAs) have been shown to have great importance not only in tumorigenesis but also in therapeutic prognosis. The aim of this study is to investigate the role of lncRNA HOTTIP in the chemo-resistance to cisplatin and gemcitabine (CG) in CCA. The upregulated expression of HOTTIP was observed in CCA patients and the upregulation was associated with therapeutic responsiveness and prognosis. HOTTIP silencing powerfully increased the chemotherapy sensitivity through weakening proliferation and colony formation and increasing apoptosis. Subsequently, miR-637 was identified as the functional target of HOTTIP, since mechanically it could be targeted by HOTTIP and functionally its overexpression dismissed the changes by HOTTIP silencing in vitro and in vivo. Moreover, LIM and SH3 domain protein 1 (LASP1) could be targeted and regulated by miR-637. In all, HOTTIP modulates the sensitivity to CG in CCA through the HOTTIP/miR-637/LASP1 regulatory axis, providing a new opportunities for CCA treatment.

Background: Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, largely due to its insidious onset, aggressive progression, and limited therapeutic options, resulting in poor patient prognosis. The lack of reliable prognostic biomarkers has significantly impeded precise patient stratification and personalized treatment. Methods: Presently, we integrated transcriptomic, methylomic, and clinical data from The Cancer Genome Atlas and applied a systematic combination of hundreds of machine learning algorithms to develop and validate a multidimensional prognostic signature. Results: A robust 10-gene panel of methylation-related differentially expressed genes (mrDEGs) containing DCXR, LBP, POU2AF1, SLC16A4, CALML3, MAD2L1, PPP1R14D, S100A10, SGCB, and TMEM45A was identified. This signature significantly outperformed conventional clinicopathological parameters in predicting overall survival and demonstrated consistent robustness across multiple independent validation cohorts. Further, the differential expression of these key mrDEGs was confirmed in an independent cohort of 10 paired HCC tumor and adjacent non-tumor tissues using quantitative real-time Polymerase Chain Reaction (PCR) and western blotting, corroborating the reliability and clinical relevance of our findings. Additionally, single-cell RNA sequencing and spatial transcriptomics analyses revealed that these mrDEGs are closely associated with immune cell populations, cancer-associated fibroblasts, and metabolic pathways, contributing to the regulation of the tumor microenvironment. High-risk patients exhibited an immunosuppressive microenvironment and elevated Tumor Immune Dysfunction and Exclusion scores, indicative of enhanced tumor stemness and immune evasion potential. Conclusion: This integrative multi-omics prognostic tool, combining genetic, epigenetic, and microenvironmental information, provides a more precise model for risk stratification and prognosis prediction, offering a valuable framework for individualized therapeutic decision-making and the development of novel targeted interventions, ultimately aiming to improve clinical outcomes for HCC patients.