Causality of immune cells on primary sclerosing cholangitis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies have indicated that immune dysregulation in primary sclerosing cholangitis (PSC) primarily involves intestinal-derived immune cells. However, the causal relationship between peripheral blood immune cells and PSC remains insufficiently understood. Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was implemented to determine the causal effect between PBC and 731 immune cells. All datasets were extracted from a publicly available genetic database. The standard inverse variance weighted (IVW) method was selected as the main method for the causality analysis. Cochran's Q statistics and MR-Egger intercept were performed to evaluate heterogeneity and pleiotropy. Results: In forward MR analysis, the expression ratios of CD11c on CD62L+ myeloid DC (OR = 1.136, 95% CI = 1.032-1.250, p = 0.009) and CD62L-myeloid DC AC (OR = 1.267, 95% CI = 1.086-1.477, p = 0.003) were correlated with a higher risk of PSC. Each one standard deviation increase of CD28 on resting regulatory T cells (Treg) (OR = 0.724, 95% CI = 0.630-0.833, p < 0.001) and CD3 on secreting Treg (OR = 0.893, 95% CI = 0.823-0.969, p = 0.007) negatively associated with the risk of PSC. In reverse MR analysis, PSC was identified with a genetic causal effect on EM CD8+ T cell AC, CD8+ T cell AC, CD28- CD127- CD25++ CD8+ T cell AC, CD28- CD25++ CD8+ T cell AC, CD28- CD8+ T cell/CD8+ T cell, CD28- CD8+ T cell AC, and CD45 RA- CD28- CD8+ T cell AC. Conclusion: Our study indicated the evidence of causal effects between PSC and immune cells, which may provide a potential foundation for future diagnosis and treatment of PSC.

Comparing the effects of aquatic-based exercise and land-based exercise on balance in older adults: a systematic review and meta-analysis.

BACKGROUND: Balance plays a crucial role in the daily activities of older adults. Aquatic-based exercises (AE) are widely conducted as an alternative to land-based exercises (LE). Previous studies have compared AE and LE as effective ways to improve balance and have yielded inconsistent results. Therefore, this review aimed to compare the effects of AE and LE on balance function in older adults. METHODS: Electronic databases, including PubMed, Web of Science, Scopus, and Embase, were searched. Randomized controlled trials published from January 2003 to June 2023 were included following predetermined criteria. Data extraction was carried out by two independent reviewers. Data synthesis was conducted using RevMan 5.3 software. The fixed-effect model or random-effect model was chosen based on the results of the heterogeneity test. Meta-analysis for the effect sizes of balance outcomes was calculated as standardized mean difference (SMD) with 95% confidence intervals (CI). The quality of the included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. This review was registered at PROSPERO CRD42023429557. RESULTS: A total of 29 studies involving 1486 older adults (with an average age of 66.2 years) were included. Meta-analysis results indicated that AE could improve balance ability based on two tests: the Berg balance scale (BBS: SMD = 1.13, 95% CI 0.25 to 2.00, p = 0.01, I2 = 94%) and the 30-s chair stand test (30 CST: SMD = 2.02, 95% CI 0.50 to 3.54, p = 0.009, I2 = 96%). However, there were no significant differences between the AE group and the LE group in terms of the 6-min walking test (6 MWT: SMD = 0.13, 95% CI -0.16 to 0.43, p = 0.38, I2 = 62%) and time up to go test (TUGT: SMD = 0.44, 95% CI -0.44 to 0.91, p = 0.07, I2 = 85%). Older adults with different health conditions have different gains in different balance measurements after AE intervention and LE intervention. CONCLUSIONS: Although this was influenced by participant health status, transfer effects, sample size, and other factors, AE offers better benefits than LE for improving balance function in older adults.

Predicting prognosis in intrahepatic cholangiocarcinoma by the histopathological features.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous liver tumor. The associations between histopathological feature and prognosis of ICC are limited. The present study aimed to investigate the prognostic significance of glandular structure and tumor budding in ICC. METHODS: Patients received radical hepatectomy for ICC were included. Glandular structure and tumor budding were detected by Hematoxylin-eosin staining. The Kaplan-Meier method and the Cox proportional hazards regression model were used to calculate the survival and hazard ratio. Based on the results of multivariate analysis, nomograms of OS and DFS were constructed. C-index and Akaike information criterion (AIC) were used to assess accuracy of models. RESULTS: A total of 323 ICC patients who underwent surgery were included in our study. Glandular structure was associated with worse overall survival (OS) [hazard ratio (HR): 2.033, 95% confidence interval (CI): 1.047 to 3.945] and disease-free survival (DFS) [HR: 1.854, 95% CI: 1.082 to 3.176]. High tumor budding was associated with worse DFS [HR: 1.636, 95%CI: 1.060 to 2.525]. Multivariate analysis suggested that glandular structure, tumor number, lymph node metastasis, and CA19-9 were independent risk factors for OS. Independent predictor factors for DFS were tumor budding, glandular structure, tumor number, and lymph node metastasis. The c-index (0.641 and 0.642) and AIC (957.69 and 1188.52) showed that nomograms of OS and DFS have good accuracy. CONCLUSION: High tumor budding and glandular structure are two important histopathological features that serve as prognostic factors for ICC patients undergoing hepatectomy.

A novel model for predicting the prognosis of postoperative intrahepatic cholangiocarcinoma patients.

Intrahepatic cholangiocarcinoma (ICC) accounts for 20% of liver malignancies with a 5-year survival rate of 35% at best with limited prognostic predictors. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers. In this study, we developed a modified prognostic model from LIPI called intrahepatic immune prognostic index (IIPI) for ICC. A retrospectively study was conducted at Liver Transplant Center of West China Hospital between January 2015 and January 2023. Hematological factors and clinical features of ICC patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated. In this study, derived neurtrophil to lymphocyte ratio (dNLR), arbohydrate antigen199 (CA199) and carcinoembryonic antigen (CEA) have higher AUC values. LIPI was composed of dNLR and was further modified by combing CA199 and CEA, forming the IIPI. The IIPI consists of four grades which are None, Light, Moderate and Severe. Compared to other prognostic factors, IIPI exhibited better ability to predict overall survival. The multivariate analysis indicated that cirrhosis, differentiation, hilar invasion and IIPI were independent prognostic factors for ICC patients. An IIPI-based nomogram was also established and could predict the overall survival. In addition, the subgroup analyses based on clinical prognostic factors showed that the IIPI exhibited excellent prognostic influence. IIPI model is suitable for predicting the prognosis of postoperative ICC patients. Further research is needed to explore the relationship between postoperative recurrence and metastasis of ICC patients and IIPI.

Effect of PIVKA-II and AFP secretion status on early recurrence of hepatocellular carcinoma after open and laparoscopic surgery.

BACKGROUND: Prothrombin induced by vitamin K absence-II (PIVKA-II) and Alpha-fetoprotein (AFP) have been widely used as diagnostic markers in hepatocellular carcinoma (HCC), but the prognostic values of the two serum markers and their clinical usefulness in patient selection for different surgical approaches remain largely unclear. METHODS: HCC patients received surgical treatment between 2015 and 2019 were included. Patients were divided into four statuses according to the serum PIVKA-II and AFP secretion status: PIVKA-II (-) AFP (-) (status 1); PIVKA-II (+) AFP (-) (status 2); PIVKA-II (-) AFP (+) (status 3); PIVKA-II (+) AFP (+) (status 4). Kaplan-Meier analyses were conducted to compare the survivals of the four groups and the HCC patients received different surgical interventions; time-dependent AUC curves were introduced to evaluate the prognostic value of the PIV-AFP status; Cox regression model was used to identify prognostic indexes for overall survival (OS) and recurrence-free survival (RFS). RESULTS: A total of 518 patients were included. Patients with PIVKA-II (+) and APF (+) presented significantly decreased OS and RFS comparing to the other statuses. The areas under ROC curves of PIV-AFP status in predicting OS and RFS were superior to the PIVKA-II or the AFP alone. The HCC patients in early stages with PIVKA-II (+) and APF (+) had worse RFS when received laparoscopic hepatectomy than those who received open hepatectomy, whereas there was no difference in other secretion statuses. The PIVKA-II (+) and AFP (+) secretion status was an independent risk factor for OS, RFS. CONCLUSIONS: The PIV-AFP secretion status is of favorable clinical utility in predicting the OS and RFS of the HCC patients; extra caution is needed when applicated the laparoscopic approach in the HCC patients with PIVKA-II (+) and AFP (+).

LI-RADS LR-5 on contrast-enhanced ultrasonography has satisfactory diagnostic specificity for hepatocellular carcinoma: a systematic review and meta-analysis.

Background: The Liver Imaging Reporting and Data System (LI-RADS) for contrast-enhanced ultrasonography (CEUS) was invented to define suspected liver nodules based on their imaging characteristics. Among the categories of nodules of LI-RADS for CEUS, LR-5 is generally considered to be definitely malignant; however, the exact diagnostic performance of this liver nodule category has varied between different studies. Therefore, we performed this systematic review and meta-analysis to calculate the pooled diagnostic sensitivity, specificity based on important data extracted from some influential clinical studies. Methods: A preliminary search of national and international databases, including PubMed/Ovid Medline, Embase, Cochrane Library, Web of Science, and Wan Fang Data, for relevant studies on CEUS LI-RADS LR-5 published between January 2017 and June 2021 was conducted. A literature screening and selection process was undertaken to evaluate the relevance of the articles, and studies deemed eligible for inclusion in the review were subsequently identified. The updated Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was applied as the main method to assess the risk of bias and applicability of the studies. A meta-analysis of the diagnostic sensitivity and specificity of CEUS LI-RADS LR-5 was performed using the free software, Meta-DiSc 1.4 (Ramóny Cajal Hospital, Madrid, Spain). The area under curve (AUC) was calculated to help determine the diagnostic efficiency. A meta-regression analysis was also performed to identify factors that could have contributed to heterogeneity between the studies. Results: Twelve studies with 20 observations focused on investigating the relative diagnostic performance of the CEUS LI-RADS LR-5 category for hepatocellular carcinoma (HCC) detection were finally recruited into the systematic review and meta-analysis. The pooled diagnostic sensitivity was 0.71 [95% confidence interval (CI): 0.69-0.72], with heterogeneity (I2) of 88.4%, and the pooled specificity was 0.93 (95% CI: 0.92-0.95), with an I2 of 71.2%. Study heterogeneity was observed and statistically correlated with the number of centers and the reference standard. Conclusions: The CEUS LI-RADS LR-5 category has satisfactory diagnostic efficacy for HCC, as evidenced by an acceptable diagnostic sensitivity of 0.71 and a good diagnostic specificity of 0.93.

Adequate lymph node dissection is essential for accurate nodal staging in intrahepatic cholangiocarcinoma: A population-based study.

PURPOSE: To comprehensively investigate the implications of lymph node dissection (LND) and the prognostic impact of the number of lymph node (LN) metastases on survival in intrahepatic cholangiocarcinoma (ICC) using a large-scale study. METHODS: Patients who underwent surgical resection for ICC between 2004 and 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) registries. The Kaplan-Meier and log-rank tests were used to compare cancer-specific survival (CSS) and overall survival (OS) between different groups. Propensity score matching (PSM) and subgroup analyses were performed to balance potential confounding factors. A multivariate Cox proportional hazards regression model was used to identify prognostic factors of survival outcomes. Restricted cubic splines fitted in the Cox proportional hazard regression models were also conducted to examine associations between continuous variables and outcomes. RESULTS: In all, 1028 patients were enrolled. There were 652 (63.4%) patients undergoing LND, with lymph node metastasis (LNM) confirmed in 212 (32.5%) cases. Patients receiving LND did not show better survival outcomes than those receiving non-LND (NLND). We divided the LND group into two subgroups: patients with LNM (+) and those without LNM (-). Among these three groups, patients with LNM experienced the worst CSS and OS, while NLND patients had similar survival times to LNM (-) patients. Restricted cubic spline analysis indicated that an increased number of LNM was associated with a decreased chance of survival (p < 0.001). Patients who received LND were further categorized as having no nodal metastasis (N0), 1-2 LNM (N1), or ≥3 LNM (N2) according to the number of LNM. The Kaplan-Meier curves showed that the mortality risk of patients with N0, N1, and N2 disease (median CSS, N0 50.0 vs. N1 22.0 vs. N2 14.0 months; median OS, N0 46.0 vs. N1 21.0 vs. N2 14.0 months, all p < 0.01) increased significantly, except for patients who had <6 LNs harvested. On multivariable survival analysis, a higher nodal stage (N1 vs. N0: CSS, hazard ratio [HR] 2.135, 95% CI 1.636-2.788, p < 0.001; OS, HR 2.100, 95% CI 1.624-2.717, p < 0.001; N2 vs. N0: CSS, HR 4.027, 95% CI 2.791-5.811, p < 0.001; OS, HR 3.678, 95% CI 2.561-5.282, p < 0.001) was an independent prognostic risk factor for survival. CONCLUSIONS: Despite the lack of a clear survival benefit of LND in patients with ICC, a significant positive association between the number of LNM and poor outcomes was observed. We still suggest adequate LND by examining at least six LNs to ensure precise staging. On this basis, the recently proposed nodal classification of N0, N1, and N2 stages may also allow better prognostic stratification of ICC patients.

LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/ß-catenin activation via interacting with hnRNPC.

BACKGROUND: Hepatocellular carcinoma (HCC) is the world's third leading cause of cancer-related death; due to the fast growth and high prevalence of tumor recurrence, the prognosis of HCC patients remains dismal. Long non-coding RNA CEBPA-DT, a divergent transcript of the CCAAT Enhancer Binding Protein Alpha (CEBPA) gene, has been shown to participate in multiple tumor progression. However, no research has established its cancer-promoting mechanism in HCC yet. METHODS: CEBPA-DT was identified in human HCC tissues through RNA sequencing. The expression level of CEBPA-DT was assessed by quantitative real-time PCR. The biological effects of CEBPA-DT were evaluated in vitro and in vivo through gain or loss of function experiments. RNA fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were applied to investigate the downstream target of CEBPA-DT. Immunofluorescence, subcellular protein fractionation, western blot, and co-immunoprecipitation were performed to analyze the subcellular location of ß-catenin and its interaction with Discoidin domain-containing receptor 2 (DDR2). RESULTS: CEBPA-DT was upregulated in human HCC tissues with postoperative distant metastasis and intimately related to the worse prognosis of HCC patients. Silencing of CEBPA-DT inhibited the growth, migration and invasion of hepatoma cells in vitro and in vivo, while enhancement of CEBPA-DT played a contrasting role. Mechanistic investigations demonstrated that CEBPA-DT could bind to heterogeneous nuclear ribonucleoprotein C (hnRNPC), which facilitated cytoplasmic translocation of hnRNPC, enhanced the interaction between hnRNPC and DDR2 mRNA, subsequently promoted the expression of DDR2. Meanwhile, CEBPA-DT induced epithelial-mesenchymal transition (EMT) process through upregulation of Snail1 via facilitating nuclear translocation of ß-catenin. Using DDR2 inhibitor, we revealed that the CEBPA-DT induced the interaction between DDR2 and ß-catenin, thus promoting the nuclear translocation of ß-catenin to activate transcription of Snail1, contributing to EMT and HCC metastasis. CONCLUSIONS: Our results suggested that CEBPA-DT promoted HCC metastasis through DDR2/ß-catenin mediated activation of Snail1 via interaction with hnRNPC, indicating that the CEBPA-DT-hnRNPC-DDR2/ß-catenin axis may be used as a potential therapeutic target for HCC treatment.

A novel nutritional score based on serum triglyceride and protein levels predicts outcomes of intrahepatic cholangiocarcinoma after curative hepatectomy: A multi-center study of 631 patients.

Background: High serum triglyceride (STG) level is a well-established pathogenic factor for cardiovascular diseases and is associated with the risk of various malignancies. Nevertheless, the role of STG level in intrahepatic cholangiocarcinoma (ICC) remains uncertain. Methods: A total of 631 ICC patients treated with curative hepatectomy in two centers (517 in the discovery set and 114 in the validation set) were retrospectively analyzed. Kaplan-Meier survival analysis was used to assess the outcomes of the patients with different STG levels. Time-dependent receiver operating characteristic (ROC) analysis was conducted to compare the prognostic value of STG with other established indexes. The Triglyceride-Albumin-Globulin (TAG) grade was introduced and evaluated using the time-dependent area under curves (AUC) analysis and decision curve analysis (DCA). Results: Patients with increased STG levels and decreased albumin-globulin score (AGS) were correlated with improved overall survival (OS) and recurrence-free survival (RFS). STG level ≥ 1 mmol/L was an independent protective factor for surgically treated ICC patients. The predictive value of the TAG grade was superior to the STG or the AGS alone. In decision curve analysis, the net benefits of the TAG grade in the discovery and validation set were higher than STG and AGS. Conclusion: The current study presented strong evidence that ICC patients with higher preoperative STG levels had preferred long-term surgical outcomes. The novel nutritional score based on serum triglyceride, albumin and globulin levels was inextricably linked to the prognosis of the surgically treated ICC patients. Evaluation of the TAG grade before curative hepatectomy may be beneficial for risk stratification and clinical decision support.

IL-6-induced cGGNBP2 encodes a protein to promote cell growth and metastasis in intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: IL-6-induced tumor progression has been well established through the induction of antiapoptotic and proliferative genes. However, whether other mechanisms such as IL-6 regulation of circular RNAs (circRNAs) may also contribute to tumor development remains unknown. APPROACH AND RESULTS: High-throughput RNA sequencing was used to identify the differentially expressed circRNAs on IL-6 stimulation in intrahepatic cholangiocarcinoma (ICC) cells. CircRNA GGNBP2 (derived from ggnbp2 gene, termed as cGGNBP2) was up-regulated by IL-6 treatment in a time and concentration-dependent manner. The biogenesis of cGGNBP2 was regulated by RNA-binding protein DEx-H Box Helicase 9, which was also mediated by IL-6 exposure. Mass spectrometry and western blotting identified a protein cGGNBP2-184aa encoded by cGGNBP2. cGGNBP2-184aa promoted ICC cell proliferation and metastasis in vitro and in vivo. Mechanistically, cGGNBP2-184aa directly interacted with signal transducers and activators of transduction-3 (STAT3), phosphorylated STAT3Tyr705 , and played a positive regulatory role in modulating IL-6/STAT3 signaling. IL-6/cGGNBP2-184aa/STAT3 formed a positive feedback loop to sustain constitutive activation of IL-6/STAT3 signaling. Elevated cGGNBP2 expression was correlated with poor prognosis of patients with ICC and was identified as an independent risk factor for patient prognosis. CONCLUSIONS: Our study demonstrates that cGGNBP2-184aa, a protein encoded by IL-6-induced cGGNBP2, formed a positive feedback loop to facilitate ICC progression and may serve as an auxiliary target for clinical IL-6/STAT3-targeting treatments in ICC.

Laparoscopic Pancreaticoduodenectomy Versus Conventional Open Approach for Patients With Pancreatic Duct Adenocarcinoma: An Up-to-Date Systematic Review and Meta-Analysis.

BACKGROUND: To compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic versus open pancreaticoduodenectomy (LPD vs. OPD), we performed a meta-analysis of currently available propensity score matching studies and large-scale retrospective cohorts to compare the safety and overall effect of LPD to OPD for patients with PDAC. METHODS: A meta-analysis was registered at PROSPERO and the registration number is CRD42021250395. PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Data on operative times, blood loss, 30-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien-Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, overall survival, and long-term survival) were subjected to meta-analysis. RESULTS: Overall, we identified 10 retrospective studies enrolling a total of 11,535 patients (1,514 and 10,021 patients underwent LPD and OPD, respectively). The present meta-analysis showed that there were no significant differences in overall survival time, 1-year survival, 2-year survival, 30-day mortality, Clavien-Dindo ≥3 complications, POPF, DGE, PPH, and lymph node dissection between the LPD and OPD groups. Nevertheless, compared with the OPD group, LPD resulted in significantly higher rate of R0 resection (OR: 1.22; 95% CI 1.06-1.40; p = 0.005), longer operative time (WMD: 60.01 min; 95% CI 23.23-96.79; p = 0.001), lower Clavien-Dindo grade ≥III rate (p = 0.02), less blood loss (WMD: -96.49 ml; 95% CI -165.14 to -27.83; p = 0.006), lower overall morbidity rate (OR: 0.65; 95% CI 0.50 to 0.85; p = 0.002), shorter LOS (MD = -2.73; 95% CI -4.44 to -1.03; p = 0.002), higher 4-year survival time (p = 0.04), 5-year survival time (p = 0.001), and earlier time to starting adjuvant chemotherapy after surgery (OR: -10.86; 95% CI -19.42 to -2.30; p = 0.01). CONCLUSIONS: LPD is a safe and feasible alternative to OPD for patients with PDAC, and compared with OPD, LPD seemed to provide a similar OS. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

A Novel Nomogram Based on Hepatic and Coagulation Function for Evaluating Outcomes of Intrahepatic Cholangiocarcinoma After Curative Hepatectomy: A Multi-Center Study of 653 Patients.

BACKGROUND AND AIMS: Hepatic and coagulation function are routine laboratory tests prior to curative hepatectomy. The prognostic value of gamma-glutamyl transpeptidase (GGT) to platelet ratio (GPR) and international normalized ratio (INR) in surgically treated patients with intrahepatic cholangiocarcinoma (ICC) remains unclear. METHODS: ICC patients received curative hepatectomy in two west China centers were included. Time-dependent ROC curves were conducted to compare established indexes with prognostic value for ICC. GPR-INR score was introduced and evaluated using the Time-dependent AUC curve and Kaplan-Meier survival analysis. A novel nomogram based on the GPR-INR score was proposed; Harrell's C-index, calibration curve and decision curve analysis were used to assess this nomogram. RESULTS: A total of 653 patients were included. The areas under ROC curves of GPR and INR in OS and RFS were superior to other indexes. Patients with a high GPR-INR score (1,2) presented significantly decreased overall survival (OS) and recurrence-free survival (RFS); GPR-INR sore, along with several clinicopathological indexes were selected into the nomogram, the calibration curve for OS probability showed good coincidence between the nomogram and the actual surveillance. The C-index of the nomogram was 0.708 (derivation set) and 0.746 (validation set), which was more representative than the C-indexes of the GPR-INR score (0.597, 0.678). In decision curve analysis, the net benefits of the nomogram in derivation and validation set were higher than Barcelona Clinic Liver Cancer staging (BCLC) classification and American Joint Committee on Cancer (AJCC) TNM 8th staging system. CONCLUSIONS: The proposed nomogram generated superior discriminative ability to established staging systems; it is profitable to applicate this nomogram in clinical practice.

Circular RNA circDLC1 inhibits MMP1-mediated liver cancer progression via interaction with HuR.

Rationale: circular RNAs (circRNAs) have been demonstrated to play a crucial role in cancer progression. KIAA1429, a key component of the m6A methyltransferase complex, has recently been reported to promote hepatocellular carcinoma (HCC) progression by regulating the m6A methylation. The aim of present study is to investigate the role of circular RNAs in KIAA1429-mediated HCC progression. Methods: RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (m6A-seq) were utilized to identify KIAA1429-regulated circRNAs. The effects of circDLC1 on proliferation and metastasis of hepatoma cells were examined in vitro and in vivo. RT-qPCR was used to measure the expression of circDLC1 in HCC tissues and hepatoma cells. RNA FISH, RIP assays and biotin-labeled RNA pull-down were used to investigate the downstream effector of circDLC1. The downstream targets of circDLC1 were identified using RNA-seq. Results: Our data demonstrated that circDLC1 was downregulated in HCC tissues and closely relevant to favorable prognosis. Overexpression of circDLC1 inhibited the proliferation and motility of hepatoma cells in vitro and in vivo, while silencing of circDLC1 played the opposite role. Mechanistic investigations revealed that circDLC1 could bind to RNA-binding protein HuR, which subsequently reduced the interaction between HuR and MMP1 mRNAs, and thus inhibited the expression of MMP1, ultimately contributing to inhibition of HCC progression. Conclusion: Our work suggests that circDLC1, a downstream target of KIAA1429, is a promising prognostic marker for HCC patients, and the circDLC1-HuR-MMP1 axis may serve as a potential therapeutic target for HCC treatment.