BACKGROUND:Metabolic reprogramming is a key cancer hallmark, with dysregulated fatty acid metabolism critical for tumorigenesis and progression. The acyl-CoA synthetase long-chain (ACSL) family (ACSL1-ACSL6) catalyzes ATP-dependent activation of long-chain fatty acids into acyl-CoA, a bioactive intermediate in lipid synthesis, β-oxidation, membrane biogenesis, and signal transduction. Dysregulated ACSL expression is widespread in malignancies, but their non-metabolic functions (ferroptosis regulation, tumor immune microenvironment remodeling) and translational potential of targeted therapies remain to be systematically summarized. METHODS:This narrative review comprehensively synthesizes existing literature on the biological functions of ACSL family members in cancer. We retrieved and analyzed studies focusing on ACSL-mediated lipid metabolic reprogramming, ferroptosis modulation, and immunomodulatory effects, with particular emphasis on isoform-specific mechanisms and the context-dependent roles (pro-tumorigenic or tumor-suppressive) of the ACSL family across different cancer types. Additionally, we summarized emerging therapeutic strategies targeting ACSL isoforms and their translational potential. RESULTS:ACSL isoforms exert distinct context-dependent effects:ACSL1 promotes immunosuppressive TIME via M2 macrophage polarization;ACSL3/4 have antagonistic roles in ferroptosis;ACSL5 exerts dual effects via lipid metabolism, apoptosis, and immunity;ACSL6 involves autophagy and hematological malignancies. Dysregulation correlates with tumor progression, drug resistance, and immunotherapy response, while emerging ACSL-targeted drugs show substantial translational potential. CONCLUSIONS:The ACSL family serves as a key regulatory node integrating lipid metabolism, ferroptosis, and tumor immunity. Its isoform-specific mechanisms and context-dependent characteristics highlight its potential as a precise therapeutic target. Future research should focus on optimizing isoform-selective inhibitors, clarifying their synergistic effects with existing therapies (e.g., immune checkpoint inhibitors, radiotherapy), and validating their translational efficacy through clinical trials to advance the development of innovative cancer treatment strategies.

Protein kinases contribute to hepatocellular carcinoma (HCC) development and immune evasion, posing major challenges for HCC management. Here we show STE20/SPS1-related proline/alanine-rich kinase (SPAK) as a candidate immune exhaustion–associated gene identified through a pooled screen of protein kinases. By integrating bioinformatic analyses, data from patient cohorts, and functional studies in mouse models and cell lines, we demonstrate that elevated expression of SPAK promotes HCC progression, enhances stemness, drives immune exhaustion, and contributes to resistance to targeted therapies. Mechanistically, SPAK phosphorylates GSK3β at Ser9, thereby inhibiting proteasome-mediated degradation of c-Jun and PD-L1. Additionally, we find that DNMT3B-dependent intragenic methylation of SPAK contributes to its high expression in HCC. Notably, the SPAK inhibitor exhibits potent inhibitory effects and synergizes with PD-1 blockade to enhance antitumor efficacy. In summary, these findings establish SPAK as a driver of oncogenesis and immune exhaustion in HCC and highlight dual inhibition as a potential therapeutic strategy. Protein kinases contribute to hepatocellular carcinoma progression and immune evasion. This study identifies SPAK as a key driver of oncogenesis and immune exhaustion, showing that SPAK inhibition synergizes with anti-PD-1 therapy to enhance antitumor efficacy.

The transmembrane and coiled-coil domains 3 (TMCO3) are highly expressed in many tumors. However, the underlying mechanisms governing the way in which TMCO3 affects the progression of hepatocellular carcinoma (HCC) remain unclear. This study screens out the molecule TMCO3 with high N6-methyladenosine (m6A) modification level in tumor samples compared to the adjacent non-cancerous tissues of three pairs of HCC patients through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). Subsequently, the oncogenic effect of TMCO3 in HCC is verified through in vivo and in vitro experiments. AlkB Homolog 5 (ALKBH5), an m6A demethylase of TMCO3 is then screened out. The following experiments demonstrate that TMCO3 can activate AKT directly through the Phosphatidylinositol-3-Kinase (PI3K) pathway, thus promoting the progression of HCC. Meanwhile, the phosphorylation site on TMCO3: the 85th amino acid-serine, and mutation of this site can directly impair the activity and membrane translocation of AKT is found. Finally, the carcinogenic effect of TMCO3 is further elucidated in HCC through the orthotopic treatment model and the hydrodynamic tail vein injection treatment model. The findings can provide a potential target for targeted AKT treatment in patients with HCC and verify a possible prognostic marker in HCC.

Family with sequence similarity 134, member B (FAM134B), known for its role as an ER-phagy receptor, has been implicated in the promotion of hepatocellular carcinoma (HCC) progression through the activation of the AKT signaling pathway. However, the precise mechanism underlying FAM134B’s activation of AKT signaling remains to be elucidated. This study aimed to investigate the interaction between FAM134B and DEAD-box helicase 3 X-linked (DDX3X) and its implications for HCC. We found that FAM134B interacts with DDX3X, preventing its proteasomal degradation by reducing K48-linked polyubiquitination and enhancing K63-linked polyubiquitination. This stabilization of DDX3X is crucial for AKT signaling activation, as DDX3X is known to promote the transcription of Rac Family Small GTPase 1 (Rac1), a key activator of the AKT pathway. Our results confirmed that FAM134B activates AKT signaling through the DDX3X-Rac1-AKT axis in HCC. Furthermore, we observed that DDX3X is upregulated in HCC and contributes to tumor progression. Interestingly, DDX3X not only activates AKT signaling but also increases FAM134B expression by enhancing its transcriptional activity, suggesting a positive feedback loop between these two proteins in HCC. Lastly, we explored the therapeutic potential of combining the DDX3X inhibitor RK-33 with FAM134B knockdown in HCC treatment. Our findings indicate that this synergistic approach may offer a promising strategy for HCC therapy.

Background and Aims:Lenvatinib is recognized as a first-line therapy for inoperable hepatocellular carcinoma (HCC) patients. Growing evidence indicates that lenvatinib resistance can be acquired in HCC cells via kinase rewiring.Approach and Results:We established acquired lenvatinib-resistant organoids and HCC cell lines. NIMA-related coiled-coil kinase 7 (NEK7) was identified as an HCC lenvatinib acquired resistance gene by kinase CRISPR-Cas9 genetic screen. Functional analyses demonstrate that NEK7 enhanced lenvatinib resistance in HCC, and NEK7 knockdown or knockout displays the antitumor effects in acquired lenvatinib HCC cells and organoids. Mechanistically, NEK7 binds to the endothelial growth factor receptor (EGFR), leading to the phosphorylation of EGFR specifically at the serine 1070 residue, which contributes to the activation of MAPK (mitogen-activated protein kinase) and PI3K/AKT (phosphoinositide 3-kinase/Akt) signaling pathways. Consistently, designed inhibitory peptides targeting the domain from amino acids 979 to 1099 were proven to inhibit phosphorylation of EGFR S1070 site and therapeutically inhibit antitumor activity of acquired lenvatinib resistance HCC.Conclusions:Our results unveil insights into the acquired lenvatinib resistance mechanism that NEK7 phosphorylates EGFR at S1070 to promote acquired lenvatinib resistance in HCC.

Dysregulation of MYC proto-oncogene, bHLH transcription factor (MYC) represents a common yet mechanistically unresolved driver of hepatocellular carcinoma (HCC). While MYC remains an elusive therapeutic target, developing strategies to promote its degradation emerges as a promising alternative approach. Here we show that vaccinia-related kinase 2 (VRK2) functions as a direct MYC-interacting kinase that stabilizes the oncoprotein through phosphorylation at Serine (Ser)281/293. This phosphorylation enables VRK2 to compete with the Skp1-Cullin-F-box protein complex containing FBXO24 (SCF-FBXO24) E3 ligase, thereby blocking MYC polyubiquitination and proteasomal degradation. The stabilized MYC-VRK2 complex amplifies transcriptional activation of protumorigenic programs, including the immune checkpoint programmed cell death ligand 1 (PD-L1) and VRK2 itself, establishing a self-reinforcing oncogenic circuit. Therapeutic inhibition of VRK2 in HCC models reduces MYC protein levels, suppresses tumor progression, and synergizes with anti- programmed cell death-1 (PD-1) immunotherapy. Our results reveal VRK2-mediated stabilization of MYC as a critical nexus linking hepatocarcinogenesis to immune evasion, proposing VRK2 kinase inhibition as a mechanism-based therapeutic strategy for MYC-driven HCC.

RETREG1/FAM134B is known for its role as a reticulophagy receptor. Our previous study established that RETREG1 is upregulated in hepatocellular carcinoma (HCC) and contributes to disease progression by activating the AKT signaling pathway. However, the specific mechanisms underlying the elevated expression of RETREG1 in HCC remain unclear. This study unveils the interaction of RETREG1 with CKAP4 and TRIM21. We demonstrated that TRIM21 ubiquitinates RETREG1 at K247 and K252, facilitating its proteasomal degradation. Conversely, CKAP4 shields RETREG1 from degradation by competitively binding to it, revealing a novel post-translational modification mechanism for RETREG1. By modulating RETREG1 expression, CKAP4, and TRIM21 intricately regulate reticulophagy. Additionally, we observed that stress-induced TRIM21 upregulation mitigates the function of RETREG1 to restore ER stress equilibrium. The oncogenic potential of CKAP4 in HCC was demonstrated using various animal models. Clinical sample analyses suggested that CKAP4 is a potential biomarker for HCC prognosis and diagnosis.Abbreviation: AKT: thymoma viral proto-oncogene; aa: amino acid; bp: base pair; CHX: cycloheximide; co-IP: co-Immunoprecipitation; CQ: chloroquine; CKAP4: cytoskeleton-associated protein 4; DKK1: dickkopf WNT signaling pathway inhibitor 1; DUBs: deubiquitinating enzymes; EBSS: Earle's balanced salt solution; EGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HCC: hepatocellular carcinoma; HFD: high-fat diet; HiTV: hyperdynamic tail vein injection; IF: immunofluorescence; IHC: immunohistochemistry; IP-MS: immunoprecipitation-mass spectrometry; LIR: LC3-interacting region; mAbs: monoclonal antibodies; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mCherry: monomeric cherry; oe: overexpression; PDX: patient-derived tumor xenograft; reticulophagy: endoplasmic reticulum selective autophagy; RETREG1: reticulophagy regulator 1; RHD: reticulon-homology domain; Tg: thapsigargin; Tm: tunicamycin; TRIM21: tripartite motif-containing 21; UB: ubiquitin; WT: wild-type.

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

Both the transforming growth factor beta (TGF-β) signaling pathway and N6-methyladenosine (m6A) modification for mRNA play an important role in hepatocellular carcinoma (HCC) progression. However, the relationship between TGF-β and m6A in hepatocellular carcinoma (HCC) remains unclear. Here, it is found that TGF-β can promote the liquid phase separation of METTL3, which further leads to the reduction of mRNA stability of ITIH1. As a secreted protein, ITIH1 can act as a ligand of integrin α5β1 to antagonize fibronectin, induce the inhibition of focal adhesion kinase signaling pathway, and inhibit the progression of HCC. In the preclinical model (mouse model, patient-derived organoid, patient-derived xenografts), purified recombinant ITIH1 (r-ITIH1) protein can be targeted for HCC. More importantly, r-ITIH1 can play a synergistic role in targeting HCC with TGF-β inhibitor. The downstream ITIH1 regulatory mechanism of TGF-β and m6A modification is revealed, and ITIH1 can be translational as a potential target for HCC.

BACKGROUND:Hepatocellular carcinoma (HCC) continues to pose a significant threat to patient survival. Emerging evidence underscores the pivotal involvement of long non-coding RNAs (lncRNAs) in the cancer process. Nevertheless, our understanding of the roles and processes of lncRNAs in HCC remains limited. METHODS:The expression level of USP27X-AS1 was assessed in an HCC patient cohort through a combination of bioinformatics analysis and qRT-PCR. Subsequent biological experiments were conducted to delve into the functional aspects of USP27X-AS1. Additional molecular biology techniques, including RNA pulldown and RNA immunoprecipitation (RIP), were employed to elucidate the potential mechanisms involving USP27X-AS1 in HCC. Finally, CUT-RUN assay and other investigations were carried out to determine the factors contributing to the heightened expression of USP27X-AS1 in HCC. RESULTS:High expression of the novel oncogene USP27X-AS1 predicted poor prognosis in HCC patients. Further investigation confirmed that USP27X-AS1 promoted the proliferation and metastasis of HCC by enabling USP7 to interact with AKT, which reduced level of AKT poly-ubiquitylation and enhanced AKT protein stability, which improves protein stabilisation of AKT and promotes the progression of HCC. Moreover, we also revealed that SP1 binds to USP27X-AS1 promoter to activate its transcription. CONCLUSIONS:Novel oncogenic lncRNA USP27X-AS1 promoted HCC progression via recruiting USP7 to deubiquitinate AKT. SP1 transcriptionally activated USP27X-AS1 expression. These findings shed light on HCC and pointed to USP27X-AS1 as a potential predictive biomarker and treatment target for the malignancy.

Integrinβ-1 (ITGB1) is a crucial member of the transmembrane glycoprotein signaling receptor family and is also central to the integrin family. It forms heterodimers with other ligands, participates in intracellular signaling and controls a variety of cellular processes, such as angiogenesis and the growth of neurons; because of its role in bidirectional signaling regulation both inside and outside the membrane, ITGB1 must interact with a multitude of substances, so a variety of interfering factors can affect ITGB1 and lead to changes in its function. Over the past 20 years, many studies have confirmed a clear causal relationship between ITGB1 dysregulation and cancer development and progression in a wide range of benign diseases and solid tumor types, which may imply that ITGB1 is a prognostic biomarker and a therapeutic target for cancer treatment that warrants further investigation. This review summarizes the biological roles of ITGB1 in benign diseases and cancers, and compiles the current status of ITGB1 function and therapy in various aspects of tumorigenesis and progression. Finally, future research directions and application prospects of ITGB1 are suggested.

Background and Aims:Cirrhosis is the precursor lesion for most hepatocellular carcinoma (HCC) cases. However, no biomarker effectively predicted HCC initiation before diagnosis by imaging. We aimed to investigate the hallmarks of immune microenvironments in healthy, cirrhotic livers and HCC tumor tissues and to identify immune biomarkers of cirrhosis-HCC transition.Methods:Expression matrices of single-cell RNA sequencing studies were downloaded and integrated with Seurat package vignettes. Clustering was performed to analyze the immune cell compositions of different sample types.Results:The cirrhotic liver and HCC tumors had distinct immune microenvironments, but the immune landscape of cirrhotic livers was not markedly modified compared with healthy livers. Two subsets of B cells and three subsets of T cells were identified in the samples. Among the T cells, naïve T cells were more prominent in the cirrhotic and healthy liver samples than in the HCC samples. In contrast, the neutrophil count was lower in cirrhotic livers. Two macrophage clusters were identified, one that actively interacted with T cells and B cells and was enriched in cirrhotic blood compared with HCC blood samples.Conclusions:Decreased naïve T cell infiltration and increased neutrophil infiltration in the liver may indicate the development of HCC in cirrhotic patients. Alterations in blood-resident immune cells may also be a sign of HCC development in cirrhotic patients. The dynamics of the immune cell subsets may serve as novel biomarkers to predict the transition from cirrhosis to HCC.

As the most important RNA epigenetic regulation in eukaryotic cells, N6-metheyladenosine (m6A) modification has been demonstrated to play significant roles in cancer progression. However, this modification in long intergenic non-coding RNAs (lincRNAs) and the corresponding functions remain elusive. Here, we showed a lincRNA LINC02551 was downregulated by AlkB Homolog 5 (ALKBH5) overexpression in a m6A-dependent manner in hepatocellular carcinoma (HCC). Functionally, LINC02551 was required for the growth and metastasis of HCC. Mechanistically, LINC02551, a bona fide m6A target of ALKBH5, acted as a molecular adaptor that blocked the combination between DDX24 and a E3 ligase TRIM27 to decrease the ubiquitination and subsequent degradation of DDX24, ultimately facilitating HCC growth and metastasis. Thus, ALKBH5-mediated LINC02551 m6A methylation was required for HCC growth and metastasis.

Abstract Background Circular RNAs (circRNAs) function as crucial regulators in multiple cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNAs in HCC remains largely unknown. Methods circTOLLIP was identified in HCC by screening of two public circRNA microarray datasets and detected in HCC cells and tissues through quantitative real-time PCR (qRT–PCR) and in situ hybridization (ISH). Gain- and loss-of-function assays were performed to confirm the biological effects of circTOLLIP on HCC in vitro and in vivo. Mechanistically, bioinformatics analysis of online databases, MS2-RNA pulldown, biotin-labeled circTOLLIP/miR-516a-5p RNA pulldown, RNA immunoprecipitation (RIP), luciferase reporter assay, fluorescence in situ hybridization assay (FISH) and RNA sequencing were used to confirm the regulation of Eukaryotic initiation factor 4A3 (EIF4A3) on circTOLLIP and the interaction among circTOLLIP, miR-516a-5p and PBX homeobox 3 (PBX3). Results circTOLLIP was significantly upregulated in HCC cells and tissues. High circTOLLIP expression was correlated with poor overall survival (OS) and disease-free survival (DFS) in patients. circTOLLIP promoted the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, EIF4A3 promoted the biogenesis of circTOLLIP without affecting its stability. Moreover, circTOLLIP sponged miR-516a-5p to elevate the expression of PBX3, thereby activating the epithelial-to-mesenchymal transition (EMT) pathway and facilitating tumor progression in HCC. Conclusions Our findings indicate that EIF4A3-induced circTOLLIP promotes the progression of HCC through the circTOLLIP/miR-516a-5p/PBX3/EMT axis.

• ⚫Peptide α-connexin carboxyl terminal peptide (ACT1) protects graft livers during cold storage by steadying cell junctions. • ⚫ACT1 reduces hepatic ischemia-reperfusion injury following transplantation. • ⚫ACT1 inhibits acute and chronic inflammation after transplantation. • ⚫The effect of ACT1 on cell junctions is long term. Ischemia-reperfusion injury is an inevitable process that the liver must go through after liver transplantation. Because of the worldwide shortage of grafts, reliable intervention strategies should be explored to protect grafts. α-Connexin carboxyl terminal peptide (ACT1), which is a synthetic peptide containing 25 amino acids, has the effect of stabilizing cell junctions. The purpose of this study was to investigate the role of ACT1 on ischemia-reperfusion injury after liver transplantation in mice. Experimental results showed that injury to livers that underwent extended cold preservation was reduced by ACT1. After 6 hours of reperfusion, ACT1-treated livers showed less necrosis and acute inflammation and the cell junctions were strengthened. Moreover, after 28 days of reperfusion, the application of ACT1 distinctly alleviated hepatic damage and later cholangiopathy as well as conspicuously consolidated the cell junctions. This study indicated that ACT1 produced affirmative effects in suppressing hepatic ischemia-reperfusion injury in liver transplantation with extended cold preservation in mice by protecting cell junctions and may be a potential strategy to extend the cold preservation time of grafts for liver transplantation.

Serous ovarian carcinoma (SOC) is a gynecological malignancy with high mortality rates. Currently, there is a lack of reliable biomarkers for accurate SOC patient prognosis. Here, we analyzed SOC RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify prognostic biomarkers. Through the pearson correlation analysis, univariate Cox regression analysis, and LASSO-penalized Cox regression analysis, we identified nine lncRNAs significantly associated with four types of RNA modification writers (m6A, m1A, APA, and A-I) and with the prognosis of SOC patients (P <0.05). Six writer-related lncRNAs were ultimately selected following multivariate Cox analysis. We established a risk prediction model based on these six lncRNAs and evaluated its prognostic value in multiple groups (training set, testing set, and entire set). Our risk prediction model could effectively predict the prognosis of SOC patients with different clinical characteristics and their responses to immunotherapy. Lastly, we validated the predictive reliability and sensitivity of the lncRNA-based model via a nomogram. This study explored the association between RNA modification writer-related lncRNAs and SOC prognosis, providing a potential complement for the clinical management of SOC patients.

Background Hepatocellular carcinoma (HCC) is a type of cancer that affects the liver and has a high mortality rate. Long non-coding RNAs (lncRNAs) dysregulation can contribute to cancer occurrence and progression, although the underlying molecular pathways are mostly unclear. HOXC-AS3 was found to be considerably overexpressed in HCC in this investigation. The goal of this work was to look into the involvement of HOXC-AS3 in HCC and the various molecular pathways that underpin it. Methods Normal liver and paired HCC tissues from HCC patients were used to evaluate HOXC-AS3 expression by qRT-PCR. The role of HOXC-AS3 in HCC was assessed both in vitro and in vivo. RNA pulldown, RIP and co-IP were used to demonstrate the potential mechanism by which HOXC-AS3 regulates the progression of HCC. Results Using qRT-PCR, it was discovered that HOXC-AS3 was substantially expressed in HCC. In vitro and in vivo, overexpression of HOXC-AS3 aided proliferation and cell cycle progression. HOXC-AS3 interacted with CDK2 to facilitate CDK2’s decreased binding to p21, resulting in enhanced CDK2 activity, which promoted the phosphorylation of Rb and the progression of HCC. Conclusions HOXC-AS3 is highly expressed in HCC and can promote the progression of HCC by interacting with CDK2. Therefore, targeting HOXC-AS3 is very likely to provide a new strategy for the treatment of HCC and for improving patient prognosis.

Background: Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined. Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1. Results: Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC. Conclusions: CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.

MicroRNAs (miRNAs) have been reported to play critical roles in the pathological development of hepatocellular carcinoma (HCC), one of the most common cancers in the world. Our study aims to explore the expression, function and mechanism of miR-631 in HCC. Our findings are that expression of miR-631 is significantly down-regulated in HCC tissue compared with that in adjacent non-cancerous tissue, and low expression of miR-631 in HCC tissue is associated with cirrhosis, multiple tumors, incomplete tumor encapsulation, poor tumor differentiation, and high TNM stage. Our test results showed that miR-631 could inhibit migration, invasion, epithelial–mesenchymal transition (EMT) and intrahepatic metastasis of HCC. Receptor-type protein tyrosine phosphatase epsilon (PTPRE) as a downstream target of miR-631 could promote migration, invasion and EMT of HCC cells. Besides, the expression of PTPRE had a negative correlation with the expression of miR-631 both in vivo and in vitro, and increasing expression of PTPRE could reverse inhibitory effects of miR-631 in HCC cells. In sum, our study first demonstrated that miR-631 targeted PTPRE to inhibit intrahepatic metastasis in HCC. We gain insights from these findings into the mechanism of miRNAs regulation in HCC metastasis and further introduce a novel therapeutic target for HCC treatment.

Human papillomavirus (HPV) infection was associated with some carcinomas, especially malignant tumors in upper digestive tract, upper respiratory tract, and genitourinary system. The mechanism of the viral transformation of normal cells is still not very clear. To investigate the tumorigenesis of epithelial cells, E6/E7-induced malignant transformation model cells were used for expression profiling analysis by performing RNA expression microarray detection. Bioinformatics analysis was applied to investigate the cellular process changes along with the E6/E7 expression in SHEE cells. The differentially expressed genes were further grouped and uploaded for Search Tool for the Retrieval of Interacting Genes analysis. The protein-protein interaction results were visualized. The hub genes and their first-neighbors genes were selected, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The obtained results demonstrated that tumor-related biological processes began to emerge during the carcinogenesis process from 48th passage to 76th passage of SHEE cells after E6/E7 expression. Ten hub genes were identified and analyzed during the E6/E7-induced tumorigenesis. This study explores the gene expression network in the progressive transformation of immortalized esophageal epithelial cells induced by E6/E7 expression. Understanding the biological processes and hub genes that first appear during the transformation will provide some clues to the mechanism of E6/E7-induced carcinogenesis of esophageal epithelial cells.