Endoscopic submucosal dissection versus surgery for T1b esophageal carcinoma: a single-center retrospective study.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery, especially for T1b SESCC. This study compared the overall survival (OS), disease-free survival (DSS), recurrence-free survival (RFS), and complication rates of both, to evaluate the value of ESD in patients with T1b SESCC. METHODS: We reviewed patients who underwent ESD (n = 47) or surgery (n = 73) for T1b SESCC at Affiliated Hospital of Nanjing University of Chinese Medicine from 2009 to 2021. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion and elderly people. RESULTS: In the ESD and surgery groups, the overall mortality rates were 0/100 and 12.3/100 person years, incidence rates of recurrence were 2.13/100 and 11/100 person years, respectively. Kaplan-Meier survival analysis revealed no significant different in OS, DSS and RFS. Charlson comorbidity index (CCI) and depth of submucosal invasion were identified as risk factors for cancer recurrence in multivariate analysis. For elderly people, no significant differences were found in OS, DSS and RFS between different treatments. CONCLUSION: ESD are related to lower complication rates and shorter hospital stay than surgery in long-term outcomes for patients with pT1b SESCC. But in pT1b-SM2 patients, we still need long-term follow-up.

Fam96a is essential for the host control of Toxoplasma gondii infection by fine-tuning macrophage polarization via an iron-dependent mechanism.

BACKGROUND: Toxoplasmosis affects a quarter of the world's population. Toxoplasma gondii (T.gondii) is an intracellular parasitic protozoa. Macrophages are necessary for proliferation and spread of T.gondii by regulating immunity and metabolism. Family with sequence similarity 96A (Fam96a; formally named Ciao2a) is an evolutionarily conserved protein that is highly expressed in macrophages, but whether it play a role in control of T. gondii infection is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we utilized myeloid cell-specific knockout mice to test its role in anti-T. gondii immunity. The results showed that myeloid cell-specific deletion of Fam96a led to exacerbate both acute and chronic toxoplasmosis after exposure to T. gondii. This was related to a defectively reprogrammed polarization in Fam96a-deficient macrophages inhibited the induction of immune effector molecules, including iNOS, by suppressing interferon/STAT1 signaling. Fam96a regulated macrophage polarization process was in part dependent on its ability to fine-tuning intracellular iron (Fe) homeostasis in response to inflammatory stimuli. In addition, Fam96a regulated the mitochondrial oxidative phosphorylation or related events that involved in control of T. gondii. CONCLUSIONS/SIGNIFICANCE: All these findings suggest that Fam96a ablation in macrophages disrupts iron homeostasis and inhibits immune effector molecules, which may aggravate both acute and chronic toxoplasmosis. It highlights that Fam96a may autonomously act as a critical gatekeeper of T. gondii control in macrophages.

A pan-cancer analysis uncovering the function of CRHBP in tumor immunity, prognosis and drug response: especially its function in LIHC.

Corticotropin-releasing hormone-binding protein (CRHBP) is involved in many physiological processes. However, it is still unclear what role CRHBP has in tumor immunity and prognosis prediction. Using databases such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Tumor Protein Database, Timer Database, and Gene Expression Profiling Interactive Analysis (GEPIA), we evaluated the potential role of CRHBP in diverse cancers. Further research looked into the relationships between CRHBP and tumor survival prognosis, immune infiltration, immune checkpoint (ICP) indicators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methylation, tumor microenvironment (TME), and drug responsiveness. The anticancer effect of CRHBP in liver hepatocellular carcinoma (LIHC) was shown by Western blotting, EdU staining, JC-1 staining, transwell test, and wound healing assays. CRHBP expression is significantly low in the majority of tumor types and is associated with survival prognosis, ICP markers, TMB, and microsatellite instability (MSI). The expression of CRHBP was found to be substantially related to the quantity of six immune cell types, as well as the interstitial and immunological scores, showing that CRHBP has a substantial impact in the TME. We also noticed a link between the IC50 of a number of anticancer medicines and the degree of CRHBP expression. CRHBP-related signaling pathways were discovered using functional enrichment. Cox regression analysis showed that CRHBP expression was an independent prognostic factor for LIHC. CRHBP has a tumor suppressor function in LIHC, according to cell and molecular biology trials. CRHBP has a significant impact on tumor immunity, treatment, and prognosis, and has the potential as a cancer treatment target and prognostic indicator.

Small-molecule agonist AdipoRon alleviates diabetic retinopathy through the AdipoR1/AMPK/EGR4 pathway.

BACKGROUND: Diabetes mellitus (DM) is a progressive disease that involves multiple organs due to increased blood glucose, and diabetic retinopathy (DR) is the main complication of DM in the eyes and causes irreversible vision loss. In the pathogenesis of diabetic vascular disease, oxidative stress caused by hyperglycemia plays an important role in Müller cell impairment. In recent years, AdipoRon, an adiponectin analog that demonstrated important physiological functions in obesity, diabetes, inflammation, and cardiovascular diseases, demonstrated cellular protection from apoptosis and reduced inflammatory damage through a receptor-dependent mechanism. Here, we investigated how AdipoRon reduced oxidative stress and apoptosis in Müller glia in a high glucose environment. RESULTS: By binding to adiponectin receptor 1 on Müller glia, AdipoRon activated 5' adenosine monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase phosphorylation downstream, thereby alleviating oxidative stress and eventual apoptosis of cells and tissues. Transcriptome sequencing revealed that AdipoRon promoted the synthesis and expression of early growth response factor 4 (EGR4) and inhibited the cellular protective effects of AdipoRon in a high-glucose environment by reducing the expression of EGR4. This indicated that AdipoRon played a protective role through the EGR4 and classical AMPK pathways. CONCLUSIONS: This provides a new target for the early treatment of DR.

Suppression of alpha-tubulin acetylation potentiates therapeutic efficacy of Eribulin in liver cancer.

Hepatocellular carcinoma (HCC) is a prevalent cancer with limited effective treatments. Eribulin mesylate is a novel chemotherapy drug that inhibits microtubule elongation and may impact the tumor microenvironment and immune pathway. This study aims to investigate the impact of changes in microtubule acetylation levels on HCC development and treatment outcomes. Clinical and molecular data were aggregated from databases, with survival analysis conducted to evaluate the relevance of microtubule acetylation. In vitro experiments using HCC cell lines and a tumor cell transplantation model in C57BL/c mice were performed to investigate the effects of microtubule acetylation on Eribulin treatment. A significant correlation was found between the level of lysine 40 acetylation of α-tubulin (acetyl-α-tubulin-lys40) and overall survival of HCC patients, with a better prognosis associated with a lower level of acetyl-α-tubulin-lys40. Knocking down ATAT1 or overexpressing HDAC6 reduced the level of acetyl-α-tubulin-lys40 and sensitized Eribulin treatment both in vitro and in vivo. In summary, acetyl-α-tubulin-lys40 was increased in HCC and was associated with a shorter overall survival of HCC patients. Reducing the level of acetyl-α-tubulin-lys40 can enhance sensitivity to Eribulin treatment both in vitro and in vivo, thereby establishing acetyl-α-tubulin-lys40 as a potential prognostic marker and predictive indicator for Eribulin treatment in HCC patients.

Is histological healing more clinically valuable than endoscopic healing in Crohn's disease?

OBJECTIVES: Small bowel (SB) endoscopic healing has not been well explored in patients with Crohn's disease (CD). This study aimed to assess the clinical utility of SB endoscopic mucosal and histological healing in patients with CD. METHODS: In total, 99 patients with CD in clinical-serological remission were retrospectively followed after they underwent colonoscopy and double-balloon enteroscopy. Time until clinical relapse (CD activity index of >150 with an increase of >70 points) and serological relapse (abnormal elevation of C-reactive protein levels) constituted the primary endpoints. RESULTS: Of the 99 patients, 75 (74.7%) exhibited colonoscopic healing and 43 (43.4%) exhibited SB endoscopic healing. Clinical relapse, serological relapse, hospitalization, and surgery occurred in 8 (18.6%), 11 (25.6%), 11 (25.6%), and 2 (4.6%) patients, respectively. Of the 43 patients who exhibited SB endoscopic healing, 21 (48.8%) achieved histological healing. Clinical relapse, serological relapse, hospitalization, and surgery occurred in 4 (19.0%), 7 (33.3%), 7 (33.3%), and 1 (4.8%) patient, respectively. There was no statistically significant difference in the number of patients who relapsed, were hospitalized, or underwent surgery between those who exhibited histological healing and those who did not. CONCLUSION: A substantial number of patients who were in clinical-serological remission did not undergo SB endoscopic healing, and the lesions increased their risk of clinical relapse. Thus, endoscopic healing may be of greater clinical value than histological healing when evaluating the remission of patients with CD.

RNautophagic regulation of DNMT3a-dependent DNA methylation by Linc00942 enhances chemoresistance in gastric cancer.

BACKGROUND: Energy balance has long been known to extend lifespans and inhibit carcinogenesis in multiple species by slowing age-related epigenetic changes while the underlying mechanisms remain largely unknown. Herein, we found that starvation activated autophagy to remodel the DNA methylation profile by inhibiting DNMT3a expression. METHODS: Illumina Infinium MethylationEPIC BeadChip and dot blot assay were performed to quantify the global DNA methylation level. Protein-RNA interactions were validated through RNA immunoprecipitation and RNA pull-down assay. In vitro and in vivo experiments were carried out to testify the effect of DNMT3a on chemoresistance. RESULTS: Autophagy is impaired in chemoresistance which was associated with differential DNA methylation and could be reversed by DNMT3a inhibition. Autophagy activation decreases the expression of DNMT3a mRNA, accompanied with the downregulation of chemoresistance-related Linc00942. Knockdown of Linc00942 reduces DNMT3a expression and genome-wide DNA methylation while Linc00942 overexpression increased DNMT3a expression and correlated hypermethylation in cancer cells and primary tumour tissues. Mechanistically, Linc00942 recruits RNA methyltransferase METTL3 to stimulate N6-methyladenosine (m6A) deposit on DNMT3a transcripts, triggering IGF2BP3/HuR to recognize modified mRNA for reinforced stability. SQSTM1/p62 recruits Linc00942 for autophagic degradation which can be abrogated after autophagy inhibition by p62 knockdown or chloroquine treatment. CONCLUSIONS: Inhibition of autophagy increases Linc00942 expression to promote chemoresistance and autophagy activation or hypomethylating agent decitabine restores chemosensitivity by reducing global DNA methylation. Overall, this study identifies a novel methylation cascade linking impaired RNautophagy to global hypermethylation in chemoresistance, and provides a rationale for repurposing decitabine to overcome chemoresistance in cancer treatment.

HSF1 promotes CD69+ Treg differentiation to inhibit colitis progression.

Regulatory T cells (Tregs) are critical for generating and maintaining peripheral tolerance. Treg-based immunotherapy is valuable for the clinical management of diseases resulting from dysregulation of immune tolerance. However, the lack of potency is a potential limitation of Treg therapy. In addition, CD69 positive-Treg (CD69+ Treg) represent a newly identified subset of Tregs with potent immune suppressive capability. Methods: Foxp3 YFP-Cre CD69 fl/fl and CD4 Cre CD69 fl/fl mice were generated to determine the relevance of CD69 to Treg. Chromatin Immunoprecipitation Assay (ChIP) and luciferase Assay were performed to detect the regulation of CD69 transcription by heat shock transcription factor 1(HSF1). Gene expression was measured by western blotting and qRT-PCR. The differentiation of naive T cells to CD69+Foxp3+ iTregs was determined by flow cytometry. The immunosuppressive ability of Tregs was analyzed by ELISA and flow cytometry. Colon inflammation in mice was reflected by changes in body weight and colon length, the disease activity index (DAI), and H&E staining of colon tissues. Results: Induced Tregs (iTregs) from CD4 Cre CD69 fl/fl mice failed to alleviate colitis. The transcription factor HSF1 interacted with the promoter of the CD69 gene to prompt its transcription during Treg differentiation. Genetic and chemical inhibition of HSF1 impaired CD69+ Treg differentiation and promoted the pathogenesis of colitis in mice. In contrast, HSF1 protein stabilized by inhibiting its proteasomal degradation promoted CD69+ Treg differentiation and alleviated colitis in mice. Moreover, adoptive transfer of iTregs with HSF1 stabilization by proteasome inhibitor (PSI) dramatically prevented the development of colitis in mice and was accompanied by decreased production of pro-inflammatory cytokines and reduced accumulation of pro-inflammatory lymphocytes in colitis tissue, whereas Tregs induced in the absence of PSI were less stable and ineffective in suppressing colitis. Conclusions: HSF1 promotes CD69+ Tregs differentiation by activating the CD69 transcription, which is critical for the immunosuppressive function of Tregs. Stabilization of HSF1 by PSIs results in the efficient generation of Tregs with high potency to treat colitis and probably other autoimmune diseases involving Tregs deficiency.

Novel insights into the mechanisms of hard exudate in diabetic retinopathy: Findings of serum lipidomic and metabolomics profiling.

Objective: Retinal hard exudates (HEs) result from lipoproteins leaking from capillaries into extracellular retinal space, and are related to decreased visual acuity in diabetic retinopathy (DR). This study aims to identify differential serum lipids and metabolites associated with HEs. Materials and methods: A cross-sectional study was conducted Jul 2017 âˆ¼ Mar 2021. We assessed the amount of HEs using standard ETDRS photographs for comparison. HEs severity was rated as "no or questionable", "moderate" or "severe". Serum samples were processed via high coverage pseudotargeted lipidomics analysis, and untargeted liquid chromatography coupled with time-of-flight mass spectrometry for metabolomics study, respectively. Weighted gene co-expression network analyses, partial least squares-discriminant analysis, and multi-receiver operating characteristic analysis were applied. Results: A total of 167 patients were included. Discovery group: 116 eyes (116 patients). Validation group: 51 eyes (51 patients). 888 lipids were detected and divided into 18 modules (MEs), ME1 âˆ¼ ME18. Lipids in ME1 significantly increased in patients with HEs in DR (NPDR and PDR combined), NPDR, and PDR, respectively. ME1 enriched to triglycerides (29%), ceramides (17%), and N-acylethanolamines (15%). A combined model of 20 lipids was the best to discriminate HEs, area under curve = 0.804, 95% confidence interval = 0.674-0.916. For metabolomics analysis, 19 metabolites and 13 pathways associated with HEs were identified. Taurine and hypotaurine metabolism, cysteine and methionine metabolism were closely related to HEs (P < 0.01). Conclusions: The lipids and metabolites identified may serve as prediction biomarkers in the early stage of HEs in DR.

Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance.

Estrogen receptor positive (ER+) breast cancer patients exhibit poorer responsiveness to nab-paclitaxel compared to ER negative (ER-) patients, with the underlying mechanisms remaining unknown. Caveolin 1 (CAV1) is a membrane invagination protein critical for the endocytosis of macromolecules including albumin-bound chemotherapeutic agents. Here, we demonstrate that ERα limits the efficacy of nab-paclitaxel in breast cancer cells while genetic or pharmacological inhibition of ERα increased the sensitivity of ER+ breast cancer cells to nab-paclitaxel. Notably, CAV1 expression inversely correlates with ERα and relates to improved clinical outcomes from nab-paclitaxel treatment. Importantly, ERα stimulates m6A dependent maturation of miR199a-5p, which is elevated in ER+ breast cancer, to inhibit CAV1 translation by antagonizing m6A modification of CAV1 mRNA. Together, our findings reveal a novel role of ERα in promoting m6A modification and subsequent maturation of miR199a-5p, which is upregulated in ER+ breast cancer, leading to the suppression of m6A modification of CAV1 and its mRNA translation, thereby contributing to nab-paclitaxel resistance. Thus, combining an ER antagonist with nab-paclitaxel could offer a promising strategy for treating ER+ breast cancer patients.

Metabolomics study of treatment response to conbercept of patients with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

Background: Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are major causes of blindness in aged people. 30% of the patients show unsatisfactory response to anti-vascular endothelial growth factor (anti-VEGF) drugs. This study aims to investigate the relationship between serum metabolome and treatment response to anti-VEGF therapy. Methods: A prospective longitudinal study was conducted between March 2017 and April 2019 in 13 clinical sites in China. The discovery group were enrolled from Shanghai General Hospital. The validation group consisted of patients from the other 12 sites. Participants received at least one intravitreal injection of 0.5 mg anti-VEGF drug, conbercept, and were divided into two groups - responders and non-responders. Serum samples of both groups were processed for UHPLC-MS/MS analysis. We constructed principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models to investigate the metabolic differences between two groups using SIMCA-P. Area under curve (AUC) was calculated to screen the biomarkers to predict treatment response. Metabolites sub-classes and enriched pathways were obtained using MetaboAnalyst5.0. Results: 219 eyes from 219 patients (nAMD = 126; PCV = 93) were enrolled. A total of 248 metabolites were detected. PCA and PLS-DA models of the discovery group demonstrated that the metabolic profiles of responders and non-responders clearly differed. Eighty-five differential metabolites were identified, including sub-classes of diacylglycerophosphocholines, lysophosphatidylcholine (LPC), fatty acids, phosphocholine, etc. Responders and non-responders differed most significantly in metabolism of LPC (p = 7.16 × 10^-19) and diacylglycerophosphocholine (p = 6.96 × 10^-17). LPC 18:0 exhibited the highest AUC, which is 0.896 with 95% confidence internal between 0.833 and 0.949, to discriminate responders. The predictive accuracy of LPC 18:0 was 72.4% in the validation group. Conclusions: This study suggests that differential metabolites may be useful for guiding treatment options for nAMD and PCV. Metabolism of LPC and diacylglycerophosphocholine were found to affect response to conbercept treatment. LPC 18:0 was a potential biomarker to discriminate responders from non-responders.

Disruption of dNTP homeostasis by ribonucleotide reductase hyperactivation overcomes AML differentiation blockade.

Differentiation blockade is a hallmark of acute myeloid leukemia (AML). A strategy to overcome such a blockade is a promising approach against the disease. The lack of understanding of the underlying mechanisms hampers development of such strategies. Dysregulated ribonucleotide reductase (RNR) is considered a druggable target in proliferative cancers susceptible to deoxynucleoside triphosphate (dNTP) depletion. Herein, we report an unanticipated discovery that hyperactivating RNR enables differentiation and decreases leukemia cell growth. We integrate pharmacogenomics and metabolomics analyses to identify that pharmacologically (eg, nelarabine) or genetically upregulating RNR subunit M2 (RRM2) creates a dNTP pool imbalance and overcomes differentiation arrest. Moreover, R-loop-mediated DNA replication stress signaling is responsible for RRM2 activation by nelarabine treatment. Further aggravating dNTP imbalance by depleting the dNTP hydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) enhances ablation of leukemia stem cells by RRM2 hyperactivation. Mechanistically, excessive activation of extracellular signal-regulated kinase (ERK) signaling downstream of the imbalance contributes to cellular outcomes of RNR hyperactivation. A CRISPR screen identifies a synthetic lethal interaction between loss of DUSP6, an ERK-negative regulator, and nelarabine treatment. These data demonstrate that dNTP homeostasis governs leukemia maintenance, and a combination of DUSP inhibition and nelarabine represents a therapeutic strategy.

The HVEM-BTLA Immune Checkpoint Restrains Murine Chronic Cholestatic Liver Injury by Regulating the Gut Microbiota.

The herpes virus entry mediator (HVEM) is an immune checkpoint molecule regulating immune response, but its role in tissue repair remains unclear. Here, we reported that HVEM deficiency aggravated hepatobiliary damage and compromised liver repair after 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced injury. A similar phenotype was observed in B and T lymphocyte attenuator (BTLA)-deficient mice. These were correlated with impairment of neutrophil accumulation in the liver after injury. The hepatic neutrophil accumulation was regulated by microbial-derived secondary bile acids. HVEM-deficient mice had reduced ability to deconjugate bile acids during DDC-feeding, suggesting a gut microbiota defect. Consistently, both HVEM and BTLA deficiency had dysregulated intestinal IgA responses targeting the gut microbes. These results suggest that the HVEM-BTLA signaling may restrain liver injury by regulating the gut microbiota.

Guanosine primes acute myeloid leukemia for differentiation via guanine nucleotide salvage synthesis.

Differentiation arrest represents a distinct hallmark of acute myeloid leukemia (AML). Identification of differentiation-induction agents that are effective across various subtypes remains an unmet challenge. GTP biosynthesis is elevated in several types of cancers, considered to support uncontrolled tumor growth. Here we report that GTP overload by supplementation of guanosine, the nucleoside precursor of GTP, poises AML cells for differentiation and growth inhibition. Transcriptome profiling of guanosine-treated AML cells reveals a myeloid differentiation pattern. Importantly, the treatment compromises leukemia progression in AML xenograft models. Mechanistically, GTP overproduction requires sequential metabolic conversions executed by the purine salvage biosynthesis pathway including the involvement of purine nucleoside phosphorylase (PNP) and hypoxanthine phosphoribosyltransferase 1 (HPRT1). Taken together, our study offers novel metabolic insights tethering GTP homeostasis to myeloid differentiation and provides an experimental basis for further clinical investigations of guanosine or guanine nucleotides in the treatment of AML patients.

Knee-ankle joint line angle: a significant contributor to high-degree knee joint line obliquity in medial opening wedge high tibial osteotomy.

BACKGROUND: Medial opening wedge high tibial osteotomy (MOWHTO) changes the knee joint inclination in the coronal plane, which can be compensated by the ankle joint. Once there is a decompensated knee joint obliquity, it can induce excessive shear force on the articular cartilage. This study aimed to investigate the capacity of the compensation by analyzing the correlation of the knee-ankle joint line angle (KAJA) and the knee joint line obliquity (KJLO). PATIENTS AND METHODS: Ninety-six patients undergoing MOWHTO were included. We measured potential predictors including preoperative or postoperative body mass index (BMI), weight-bearing line (WBL) ratio/correction amount, knee-ankle joint line angle(KAJA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibia angle (MPTA), ankle joint line obliquity (AJLO), mechanical hip-knee-ankle angle (mHKA) and joint line convergence angle (JLCA). The correlations of these predictors and postoperative KJLO were determined using Pearson correlation coefficient. The contribution of significant predictors was further analyzed using multiple linear regression. Finally, the cutoff value of the most contributing factor resulting in decompensated KJLO was derived with receiver operating characteristic (ROC) curve analysis. RESULTS: Preoperative AJLO, JLCA, MPTA, mHKA and KJLO and postoperative KAJA and MPTA correlated with postoperative KJLO. After multiple linear regression, only preoperative AJLO and JLCA and postoperative KAJA still showed significant contribution to postoperative KJLO. Postoperative KAJA made the greatest contribution. The cutoff value of postoperative KAJA was at 9.6° after ROC analysis. The incidence rate of high-grade KJLO was 69.6% when postoperative KAJA exceeded 9.6°. CONCLUSIONS: Postoperative KAJA is a significant contributor to high-grade KJLO after MOWHTO. The incidence was increased at angles greater than 9.6°. The results suggest that KAJA should be carefully assessed during preoperative planning or intraoperative evaluation. Postoperative KAJA < 9.6° can lower the rate of early high-degree KJLO.

Circ-LARP1B knockdown restrains the tumorigenicity and enhances radiosensitivity by regulating miR-578/IGF1R axis in hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Circular RNA La Ribonucleoprotein 1B (circ-LARP1B) was reported to serve as an oncogene in many types of cancers. Radiotherapy (RT) is an important element of the multimodal treatment concept in malignancies. Here, this work aimed to investigate the role of circ-LARP1B in the tumorigenesis and radiosensitivity of hepatocellular carcinoma (HCC). PATIENTS OR MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of genes and proteins. In vitro experiments were conducted using cell counting Kit-8 (CCK-8), colony formation, EDU, transwell, and tube formation assays, respectively. Dual-luciferase reporter assay was employed to identify the target relationship between miR-578 and circ-LARP1B or IGF1R (insulin-like growth factor 1 receptor). In vivo assay was performed using murine xenograft model. RESULTS: Circ-LARP1B was highly expressed in HCC tissues and cells, and high expression of circ-LARP1B was closely associated with poor prognosis. Functional experiments demonstrated that circ-LARP1B silencing impaired cell proliferation, invasion, angiogenesis and reduced radioresistance in vitro. Mechanistically, circ-LARP1B could competitively bind with miR-578 to relieve the repression of miR-578 on the expression of its target gene IGF1R. Further rescue assay confirmed that miR-578 inhibition reversed the inhibitory effects of circ-LARP1B knockdown on HCC cell malignant phenotypes and radioresistance. Moreover, miR-578 overexpression restrained tumorigenicity and enhanced radiosensitivity in HCC cells, which were attenuated by IGF1R up-regulation. Besides that, circ-LARP1B knockdown impeded tumor growth and enhanced irradiation sensitivity in HCC in vivo. CONCLUSIONS: Circ-LARP1B knockdown restrained HCC tumorigenicity and enhanced radiosensitivity by regulating miR-578/IGF1R axis, providing a new target for the treatment of HCC.