Effects of T2DM on postoperative outcome of patients with colorectal cancer: a study on the relationship between blood glucose control and survival rate.

To investigate the impact of type 2 diabetes (T2DM) on the prognosis of colorectal cancer (CRC). The data of 312 patients with CRC treated in the First Affiliated Hospital of Huzhou University from 2012 to 2018 were analyzed retrospectively. The patients were divided into a comorbidity group (n = 62) and a non-comorbidity group (n = 250) according to the presence of T2DM. The baseline data of the two groups were balanced by 1:2 propensity score matching (PSM). Kaplan-Meier analysis and Log-rank test were employed to compare the 5-year overall survival (OS) rates of patients. Cox regression model and inverse probability of treatment weighting (IPTW) were utilized to assess the influence of T2DM on 5-year OS of patients. Based on the results of Cox regression, a nomogram model of T2DM on 5-year OS of patients was constructed. A total of 62 patients in the comorbidity group and 124 patients in the non-comorbidity group were matched using PSM. The 5-year OS rate was lower in the comorbidity group than in the non-comorbidity group (82.23% VS 90.32%, P = 0.038). Subgroup analysis showed that the 5-year overall survival rate was higher in the good blood glucose control group than in the poor blood glucose control group (97.14% VS 62.96%, P<0.01). Multivariate Cox regression showed that the 5-year mortality risk in the comorbidity group was 2.641 times higher than that in the non-comorbidity group (P = 0.026). IPTW analysis showed that the 5-year risk of death in the comorbidity group was 2.458 times that of the non-comorbidity group (P = 0.019). The results showed that poor blood glucose control, BMI≥25 kg/m2, low differentiation, III/IV stage, and postoperative infection were independent factors affecting the 5-year overall survival rate of CRC patients (P<0.05). The ROC curve showed that the AUCs of the constructed model in predicting the 5-year OS in the training set and the testing set were 0.784 and 0.776, respectively. T2DM is identified as a risk factor for reduced 5-year survival among CRC patients, necessitating increased attention for this subgroup, particularly those with poor blood glucose control.

Potential targets and therapeutics for cancer stem cell-based therapy against drug resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common digestive malignancyin the world, which is frequently diagnosed at late stage with a poor prognosis. For most patients with advanced HCC, the therapeutic options arelimiteddue to cancer occurrence of drug resistance. Hepatic cancer stem cells (CSCs) account for a small subset of tumor cells with the ability of self-renewal and differentiationin HCC. It is widely recognized that the presence of CSCs contributes to primary and acquired drug resistance. Therefore, hepatic CSCs-targeted therapy is considered as a promising strategy to overcome drug resistance and improve therapeutic outcome in HCC. In this article, we review drug resistance in HCC and provide a summary of potential targets for CSCs-based therapy. In addition, the development of CSCs-targeted therapeuticsagainst drug resistance in HCC is summarized in both preclinical and clinical trials. The in-depth understanding of CSCs-related drug resistance in HCC will favor optimization of the current therapeutic strategies and gain encouraging therapeutic outcomes.

ABLIM1, a novel ubiquitin E3 ligase, promotes growth and metastasis of colorectal cancer through targeting IĸBα ubiquitination and activating NF-ĸB signaling.

Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, has been reported as a suppressor in several tumors whereas its role in colorectal cancer (CRC) remains unknown. In this study, we find that ABLIM1 is up-regulated in CRC patients and high levels of ABLIM1 predict short disease-free survival time. Knock-down of ABLIM1 in CRC cell lines by lenti-virus leads to inhibited cell proliferation, migration, and invasion capabilities in vitro and impaired growth of tumor xenografts and liver metastasis lesions in vivo, while ABLIM1 overexpression accelerates tumor growth and invasion in vitro. Mechanistically, we uncover that ABLIM1 activates the NF-ĸB/CCL-20 signaling through modulating IĸBα ubiquitination and proteasomal-mediated degradation. Further co-immunoprecipitation, in vivo and in vitro ubiquitination assays reveal ABLIM1 as a novel ubiquitin E3 ligase binding to IĸBα. Interestingly, The E3 ligase catalysis activity of ABLIM1 depends on its 402-778aa rather than its LIM domains and its interaction with IĸBα relies on the HP domain. Our findings delineate the oncogenic role of ABLIM1 in CRC progression and reveal it as a novel E3 ligase targeting IĸBα, providing new insights into the regulation of NF-ĸB signaling in tumors.

Mechanisms and targeted reversion/prevention of hepatic fibrosis caused by the non-hereditary toxicity of benzo(a)pyrene.

The effect of long term exposure to low concentrations of environmental pollutants on hepatic disorders is a major public health concern worldwide. Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants. In recent years, an increasing number of studies have focused on the deleterious effects of low concentrations of PAHs in the initiation or exacerbation of the progression of chronic liver disease. However, the underlying molecular mechanisms and effective intervention methods remain unclear. Here, we found that in hepatocytes, a low concentration of benzo(a)pyrene (B[a]P, an indicator of PAHs) chronic exposure continuously activated 14-3-3η via an epigenetic accumulation of DNA demethylation. As a "switch like" factor, 14-3-3η activated its downstream PI3K/Akt signal, which in turn promoted vascular endothelial growth factor (VEGF) production and secretion. As the characteristic fibrogenic paracrine factor regulated by B[a]P/14-3-3η, VEGF significantly induced the neovascularization and activation of hepatic stellate cells, leading to the development of hepatic fibrosis. Importantly, targeted 14-3-3η by using its specific inhibitor invented by our lab could prevent B[a]P-induced hepatic fibrosis, and could even reverse existent hepatic fibrosis caused by B[a]P. The present study not only revealed novel mechanisms, but also proposed an innovative approach for the targeted reversion/prevention of the harmful effects of exposure to PAHs on chronic liver disease.

RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3.

BACKGROUND: RP11-296E3.2 is a novel long noncoding RNA (lncRNA) associated with colorectal cancer (CRC) metastasis, that was reported in our previous clinical studies. However, the mechanisms of RP11-296E3.2 in colorectal tumorigenesis remain elusive. METHODS: RNA sequencing (RNA-seq), Fluorescence in situ hybridization (FISH), Transwell assays and others, were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vitro. In situ and metastatic tumor models were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vivo. RNA-pulldown, RNA-interacting protein immunoprecipitation (RIP), tissue microarray (TMA) assay, a luciferase reporter assay, chromatin immunoprecipitation (ChIP) and others were performed to explore the mechanisms by which RP11-296E3.2 regulates CRC tumorigenesis. RESULTS: RP11-296E3.2 was confirmed to be associated with CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, RP11-296E3.2 directly bound to recombinant Y-Box Binding Protein 1 (YBX1) and enhanced signal transducer and activator of transcription 3 (STAT3) transcription and phosphorylation. YBX1 promoted the CRC cell proliferation and migration, while knockdown of RP11-296E3.2 attenuated the effects of YBX1 on CRC cell proliferation, and metastasis and the expression of several related downstream genes. We are the first to discover and confirm the existence of the YBX1/STAT3 pathway, a pathway dependent on RP11-296E3.2. CONCLUSION: Together, these novel findings show that the RP11-296E3.2/YBX1 pathway promotes colorectal tumorigenesis and progression by activating STAT3 transcription and phosphorylation, and suggest that RP11-296E3.2 is a potential diagnostic biomarker and therapeutic target in CRC.

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent.

BACKGROUND: Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown. METHODS: The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo. RESULTS: Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitro and in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes. CONCLUSIONS: Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC.

Constructing Co@TiO2 Nanoarray Heterostructure with Schottky Contact for Selective Electrocatalytic Nitrate Reduction to Ammonia.

Electrochemical nitrate (NO3 - ) reduction reaction (NO3 - RR) is a potential sustainable route for large-scale ambient ammonia (NH3 ) synthesis and regulating the nitrogen cycle. However, as this reaction involves multi-electron transfer steps, it urgently needs efficient electrocatalysts on promoting NH3  selectivity. Herein, a rational design of Co nanoparticles anchored on TiO2  nanobelt array on titanium plate (Co@TiO2 /TP) is presented as a high-efficiency electrocatalyst for NO3 - RR. Density theory calculations demonstrate that the constructed Schottky heterostructures coupling metallic Co with semiconductor TiO2  develop a built-in electric field, which can accelerate the rate determining step and facilitate NO3 - adsorption, ensuring the selective conversion to NH3 . Expectantly, the Co@TiO2 /TP electrocatalyst attains an excellent Faradaic efficiency of 96.7% and a high NH3  yield of 800.0 µmol h-1  cm-2  under neutral solution. More importantly, Co@TiO2 /TP heterostructure catalyst also presents a remarkable stability in 50-h electrolysis test.

lncRNA TINCR Regulates Proliferation and Invasion of Hepatocellular Carcinoma Cells by Regulating the miR-375/ATG7 Axis.

Purpose: The aim of this study was to examine the role of the long noncoding RNA (lncRNA) terminal differentiation-induced noncoding RNA (TINCR) on the proliferation, apoptosis, and invasion of liver cancer cells and its mechanism. Methods: The expression of lncRNA TINCR in twenty cases of liver cancer tissues, matched liver cancer cell lines, and paracancerous tissues was analyzed by RT-PCR. CCK-8, clonogenic test, flow cytometry, and Transwell assay were used to measure the effect of lncRNA TINCR overexpression and knockdown on cell proliferation, apoptosis, and invasion. Luciferase reporter and Western blotting showed that lncRNA TINCR regulates the expression of ATG7 through miR-375, and the rescue experiment proved that lncRNA TINCR controls the invasion and proliferation of liver cancer cells via the miR-375/ATG7 signaling pathway. Furthermore, in vivo nude mouse assay demonstrated that overexpression of lncRNA TINCR inhibited liver cancer cell growth. Results: The lncRNA TINCR was highly expressed in liver cancer tissues and cell lines. Liver cancer cells responded differently to knockdown of the lncRNA TINCR compared to overexpression in terms of proliferation, colony formation, and invasion. miR-375 negatively affected the expression of ATG7. The lncRNA TINCR bound to miR-375 and influenced its expression. Transfection of miR-375 mimics greatly inhibited the inhibitory effect of lncRNA TINCR knockdown on the invasion and proliferation, whereas transfection of miR-375 inhibitor considerably reverses this effect on liver cancer cells. Overexpressing lncRNA TINCR increased liver cancer cell proliferation in vivo. Conclusion: By controlling the miR-375/ATG7 axis, the lncRNA TINCR impacts the proliferation and invasion of liver cancer cells. Therefore, the lncRNA TINCR/miR-375/ATG7 signaling axis could be a novel biological target for the diagnosis and therapy of liver cancer.

Bioinformatics Profiling and Experimental Validation of 4 Differentially-Expressed LIM Genes in the Course of Colorectal-Adenoma-Carcinoma.

BACKGROUND LIM domain proteins play crucial roles in tumors by interacting with diverse proteins. However, their roles in the course of colorectal mucosa-adenoma-carcinoma remain unclear. This study aimed to depict their dynamic expression profiles and elucidate their potential functions in this transition course. MATERIAL AND METHODS Differentially-expressed LIM proteins (DELGs) in paired adenomas, carcinomas, and mucosae were identified using the GEO dataset (GSE 117606) and validated by immunohistochemistry using our tissue microarray. Kaplan-Meier survival analysis, WGCNA, module-trait analysis, and KEGG enrichment were conducted. The correlation of DELGs expression levels with immune infiltration was assessed using the ESTIMATE package and TISCH database. The role of DELGs of interest was validated using cell proliferation, migration, and invasion assays. RESULTS Four DELGs were identified - LMO3, FHL1, NEBL, and TGFB1I1 - all of which were of significance in prognosis. Module-trait correlation and KEGG enrichment revealed their involvement in cancer-related signaling. Immunohistochemistry showed gradual downregulation of LMO3 but upregulation of NEBL in the mucosa-adenoma-carcinoma sequence. The opposite expression patterns were observed for FHL1 and TGFB1I1 in tumor epithelium and mesenchyme. High expression levels of the DELGs were correlated with increased infiltration of NK, NKT, and macrophages, except for NEBL. Importantly, LMO3 inhibited proliferation, migration, and invasion of colon epithelial cells. CONCLUSIONS This study identified 4 differentially-expressed LIM genes - LMO3, FHL1, TGFB1I1, and NEBL - and revealed they were involved in the mucosa-adenoma-carcinoma sequence via regulating cancer-related pathways, influencing epigenetic field, or affecting immune infiltration. Our findings provide new insights into the roles of LIM proteins in the course of mucosa-adenoma-carcinoma.

A Single-Center Retrospective Study to Compare the Efficacy and Safety of Modified FOLFIRINOX with S-1 as Adjuvant Chemotherapy in 71 Patients with Resected Pancreatic Carcinoma.

BACKGROUND Studies are ongoing to determine the optimal adjuvant chemotherapy (ACT) for resected pancreatic carcinoma (PC). FOLFIRINOX is a chemotherapy regimen including oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil (5-FU). S-1 is a fluoropyrimidine derivative widely used as ACT for gastrointestinal malignancy. This single-center retrospective study aimed to compare the efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) with S-1 as ACT for resected PC. MATERIAL AND METHODS A total of 71 patients with PC who accepted ACT after R0 resection between February 2016 and January 2019 were enrolled in this retrospective study. Among these patients, 34 received mFOLFIRINOX regimen chemotherapy (mFFX group), while 37 received S-1 monochemotherapy (S-1 group). The mFOLFIRINOX regimen included oxaliplatin 65 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m², 5-FU 400 mg/m², and continuous 5-FU 2400 mg/m² (for 46 h), in a 2-week schedule. The S-1 monochemotherapy (80-120 mg/day according to body surface area [BSA], in 2 divided doses for 2 week) was administrated every 3 weeks. We followed up these patients and analyzed the relapse-free survival (RFS), overall survival (OS), and chemotherapy-induced adverse events (AEs). RESULTS The mFFX group demonstrated a markedly higher 3-year RFS (P=0.0332) and OS (P=0.0346) than the S-1 group. Patients in the mFFX group experienced significantly more common and severe thrombocytopenia (P=0.0372), fatigue (P=0.0226), nausea/vomiting (P=0.0337), and diarrhea (P=0.0018). No chemotherapy-induced death was documented. CONCLUSIONS This retrospective study indicated that if dose adjustment and adverse events management are properly administrated, mFOLFIRINOX regimen chemotherapy could result in an improved survival compared with S-1 monochemotherapy for resected PC.

Effect of Shengbai Decoction on Chemotherapy-Induced Myelosuppression and Survival of Gastric Cancer Patients After Radical Resection: A Retrospective Study.

BACKGROUND Myelosuppression is one of the most common chemotherapy-induced adverse events and results in a series of clinical symptoms. This study aimed to evaluate the effect of Shengbai decoction (SD) on chemotherapy-induced myelosuppression and survival of gastric cancer (GC) patients after radical resection. MATERIAL AND METHODS We retrospectively analyzed data from 115 patients with stage II-III GC who underwent adjuvant chemotherapy after radical resection between May 2015 and June 2017 in our hospital. Among these patients, 57 received Shengbai decoction along with adjuvant chemotherapy (SD group), while 58 received adjuvant chemotherapy alone (control group). Medical records, including adverse events, the treatment completion rate of adjuvant chemotherapy, 3-year overall survival (OS), and 3-year recurrence-free survival (RFS), were compared. RESULTS Patient characteristics did not differ significantly between the 2 groups. No adverse events related to Shengbai decoction were reported in the SD group. Patients in the SD group had less neutropenia (P=0.0430), thrombocytopenia (P=0.0323), and anemia (P=0.0497). The SD group had a significantly lower probability of dose reduction (P=0.0448). The completion rate of adjuvant chemotherapy of the SD group was considerably higher than that of the control group (P=0.0398). The SD group had a significantly better 3-year RFS (P=0.0369) and 3-year OS (P=0.0455) than the control group. CONCLUSIONS Shengbai decoction effectively improved postoperative survival of patients with GC by alleviating chemotherapy-induced myelosuppression and improving the completion rate of adjuvant chemotherapy.

Long non-coding RNA TINCR promotes hepatocellular carcinoma proliferation and invasion via STAT3 signaling by direct interacting with T-cell protein tyrosine phosphatase (TCPTP).

The long non-coding RNAs (lncRNAs) participate in modulating numerous important cancer phenotypes via formation of RNA-protein complex. TINCR (terminal differentiation-induced lncRNA) modulates cancer cell behavior in many human malignancies, such as hepatocellular carcinoma (HCC). Herein, we proposed to investigate the underlying mechanism by which TINCR regulates HCC progression via formation of RNA-protein. RNA pulldown, LC-MS/MS, bioinformatics analysis, and RNA immunoprecipitation (RIP) assays were employed to identify TINCR-interacting protein TCPTP in HCC cells. The siRNAs for TINCR and TCPTP were transfected into HCC cells. The plasmids encoding full length or the 1-360 nt deletion of TINCR were generated and applied to cell transfection. The CCK-8, colony formation, EdU, wound healing along with transwell assays were employed to examine cell proliferation, apoptosis, migration, and infiltration. Real-time PCR, as well as western blot assays were employed to assess the levels of STAT3 phosphorylation and its target genes. We identified 1-360 nt region of TINCR, which directly bound with the phosphatase domain of TCPTP to inhibit its tyrosine phosphatase activity. Then, the results showed that the increasing of cell growth, migration, infiltration, and the reducing of apoptosis in TINCR-knockdown HCC cells was remarkably reversed with TCPTP silence. Additionally, Δ1-360 TINCR overexpression did not affect HCC cell growth, apoptosis, migration, infiltration, and STAT3 target genes expression. Our data revealed that TINCR directly bound TCPTP and suppressed the dephosphorylation of STAT3, thus promoting STAT3 activation and its downstream target genes in HCC progression and tumorigenicity.HighlightsLncRNA TINCR interacted with protein TCPTPLncRNA TINCR maintained STAT3 phosphorylationLncRNA TINCR affected STAT3 signaling in HCCAbbreviations:lncRNAs: long non-coding RNAs; TINCR: terminal differentiation-induced lncRNA; TCPTP: T cell protein tyrosine phosphatase; siRNA: small-interfering RNA; HCC: hepatocellular carcinoma; nt: nucleotide; LC-MS/MS: Liquid Chromatography - Tandem Mass Spectrometry; RIP: RNA immunoprecipitation; ANOVA: analysis of variance; EdU: 5-ethynyl-2'-deoxyuridine; real-time PCR: real-time polymerase chain reaction; CCK-8: cell counting kit-8; aa: amino acids; STAT3: signal transducer and activator of transcription 3.

Comprehensive transcriptome analysis of colorectal cancer risk of hyperglycemia in humans.

BACKGROUND: Epidemiological studies have found that hyperglycemia, is an independent risk factor for colorectal cancer (CRC), increasing colon cancer incidence and affecting the recurrence, metastasis, and prognosis in colon cancer patients. However, the intercorrelation between hyperglycemia and CRC risk is still unknown, In the present study, we sought to determine whether gene markers, which act in CRC with hyperglycemia, are silenced in CRC without hyperglycemia. METHODS: In order to characterize the mechanism of functional genes associated with CRC with hyperglycemia, A total 24 CRC and matched controls were sequenced. Through bioinformatics analysis includes differential expression analysis, functional enrichment, new isoform prediction and alternative splicing event identification to found biomarker genes related to CRC development. RESULTS: CRC patients with hyperglycemia were compared with patients without hyperglycemia, and we found that 21 genes were upregulated and 27 were downregulated. Further study showed that these genes are possibly of key genes involved in CRC development with hyperglycemia, such as mannan-binding lectin-associated serine protease 3 (MASP3), which has an immunological role in the activation of the complement system. Based on our comprehensive analysis, a cis-regulatory network for hyperglycemic CRC was reconstructed. CONCLUSIONS: Protein-protein interactions revealed the mechanisms of molecules involved in the interaction of hyperglycemia and cancer development. Our results provide further information on the metabolic pathway interaction with cancer pathways and elucidated the mechanisms of hyperglycemic factors function in cancer development from a transcriptomic perspective.

Maintenance Chemotherapy with S-1 Following SOX Regimen Chemotherapy Improves Prognosis of Stage 3 Gastric Cancer After D2 Gastrectomy: A 5-Year Analysis.

OBJECTIVE: To assess the effectiveness and safety of treatment consisting of maintenance chemotherapy (MCT) with S-1 following S-1 plus oxaliplatin (SOX) chemotherapy for stage 3 gastric cancer (GC) after D2 gastrectomy. METHODS: In this retrospective study, we enrolled 255 patients with stage 3 GC who underwent D2 gastrectomy between February 2011 and May 2014. The SOX regimen chemotherapy was administrated to all of the patients as adjuvant therapy. The SOX regimen consisted of S-1 (for patients with a body surface area [BSA] of less than 1.25 m2, 80 mg/d; 100 mg/d for BSA=1.25 m2- <1.5 m2, and 120 mg/d for BSA≥1.5 m2, in 2 divided doses for 14 d) and oxaliplatin (130 mg/m2 given on Day 1), repeated every 21 d for 8 cycles. Following SOX chemotherapy, 122 of these patients received maintenance chemotherapy (the MCT group) with S-1, whereas 133 patients (the control group) received no MCT. The MCT consisted of S-1 (80, 100, or 120 mg daily based on BSA, in 2 divided doses for 14 d), repeated every 21 d for 8 cycles at most. The chemotherapy was discontinued if unacceptable toxicity or disease progression occurred or upon the request of the patient. All cases were followed up, and overall survival (OS), recurrence-free survival (RFS), and toxicities were compared. RESULTS: The MCT group exhibited a distinctly higher 5-year OS (P=0.0425) and RFS (P=0.0479) than those of the control group. The incidence of hand-foot syndrome was markedly greater in the MCT group (P=0.0026). No toxicity-related death occurred. CONCLUSION: Maintenance chemotherapy with S-1 following the SOX regimen chemotherapy provides significant survival benefit for stage 3 GC after D2 gastrectomy.

Hypoxia promotes the migration and invasion of human hepatocarcinoma cells through the HIF-1α-IL-8-Akt axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. The 5-year survival rate remains low despite considerable research into treatments of HCC, including surgery, radiotherapy and chemotherapy. Many mechanisms within HCC still require investigation, including the influence of hypoxia, which has a crucial role in many cancers and is associated with metastasis. Hypoxia inducible factor-1α (HIF-1α) is known to regulate the expression of many chemokines, including interleukin-8 (IL-8), which is associated with tumor metastasis. Although many studies have reported that HIF-1α is associated with HCC migration and invasion, the underlying mechanisms remain unknown. METHODS: The expression level of HIF-1α was determined in HCC cells. The correlation of IL-8 and HIF-1α expressions was assessed via knockdown of HIF-1α. HCC cells were also used to assess the influence of HIF-1α on HCC cell migration and invasion. LY294002, an inhibitor of the Akt pathway, was used to confirm the associated signaling pathways. RESULTS: We observed a significant attenuation of cell migration and invasion after silencing of HIF-1α. Exogenously expressing IL-8 restored migration and invasion. Akt was found to be involved in this process. CONCLUSION: Hypoxia promotes HCC cell migration and invasion through the HIF-1α-IL-8-Akt axis.