Role of LncRNA H19 in tumor progression and treatment.

As one of the earliest discovered lncRNA molecules, lncRNA H19 is usually expressed in large quantities during embryonic development and is involved in cell differentiation and tissue formation. In recent years, the role of lncRNA H19 in tumors has been gradually recognized. Increasing evidence suggests that its aberrant expression is closely related to cancer development. LncRNA H19 as an oncogene not only promotes the growth, proliferation, invasion and metastasis of many tumors, but also develops resistance to treatment, affecting patients' prognosis and survival. Therefore, in this review, we summarise the extensive research on the involvement of lncRNA H19 in tumor progression and discuss how lncRNA H19, as a key target gene, affects tumor sensitivity to radiotherapy, chemotherapy and immunotherapy by participating in multiple cellular processes and regulating multiple signaling pathways, which provides a promising prospect for further research into the treatment of cancer.

Killing two birds with one stone: Abscopal effect mechanism and its application prospect in radiotherapy.

Abscopal effects are characterized by the emergence of neoplasms in regions unrelated to the primary radiation therapy site, displaying a gradual attenuation or regression throughout the progression of radiation therapy, which have been of interest to scientists since Mole's proposal in 1953. The incidence of abscopal effects in radiation therapy is intricately linked to the immune system, with both innate and adaptive immune responses playing crucial roles. Biological factors impacting abscopal effects ultimately exert their influence on the intricate workings of the immune system. Although abscopal effects are rarely observed in clinical cases, the underlying mechanism remains uncertain. This article examines the biological and physical factors influencing abscopal effects of radiotherapy. Through a review of preclinical and clinical studies, this article aims to offer a comprehensive understanding of abscopal effects and proposes new avenues for future research in this field. The findings presented in this article serve as a valuable reference for researchers seeking to explore this topic in greater depth.

The assessment of circulating tumor DNA associated with Wnt/ß-catenin signaling pathway as a diagnostic tool for liver cancer: a systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) in peripheral blood has become a promising noninvasive biomarker. However, the diagnostic potential of Wnt/ß-catenin signaling pathway-related ctDNA for liver cancer is controversial. Here, we aimed to access the diagnostic potential and clinicopathological features of Wnt/ß-catenin signaling pathway-related ctDNA in liver cancer and provide data support for its clinical diagnosis and treatment. METHODS: A comprehensive literature search was conducted to identify the relevant studies. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. The bivariate linear mixed models were used. RESULTS: The AUC (area under the curve), pooled sensitivity and specificity were 0.77, 0.42 and 0.98, respectively. The findings suggested that control type, sample source, research methods and thresholds were the potential sources of heterogeneity (p < 0.05). Additionally, this study also found that there were significant correlations between the hypermethylation of Wnt/ß-catenin signaling pathway-related ctDNA and tumor size, TNM stage, distant metastasis, and HBV infection(p < 0.05). CONCLUSION: This study confirmed that Wnt/ß-catenin signaling pathway-related ctDNA had the better diagnostic potential for liver cancer and might be an effective complementary tool for serum AFP assays in the early diagnosis of liver cancer. PROSPERO: (No. CRD42023404984).[Figure: see text].

Performance optimization and nitrogen removal mechanism of up-flow partial denitrification/anammox process.

This study aimed to remediate the problems of sludge floating and uneven mass transfer in up-flow partial denitrification/anammox (PDA) reactors and dissect the nitrogen removal mechanism. Two up-flow PDA reactors were operated, whereby in R1 combined biological carriers were added, while in R2 mechanical stirring was applied, the reactors were inoculated with PD sludge and anammox sludge. Results showed the TN removal rates at the end of the operation were 89% (R1) and 92% (R2). The addition of both strategies suppressed the occurrence of sludge upwelling and deterioration of settling performance, even when the granule diameter of the granular zone in R1 and R2 reached 1.921 and 2.006 mm, respectively. 16SrRNA sequencing revealed R1 had a higher abundance of anammox bacteria (AAOB, 14.53%-R1, 9.06%-R2, respectively), and R2 had a higher quantity of denitrifying bacteria (61.92%-R1, 67.11%-R2, respectively). And the nitrogen removal was contributed by anammox and denitrification in combination, with contributions of 82.17%, 17.83% (R1), and 85.07%, 14.93% (R2), respectively. In summary, both strategies prevented sludge flotation and uneven nitrogen mass transfer. However, mechanical agitation had a more substantial positive effect on the performance of PDA than the addition of biocarriers because it achieved a more adequate mass transfer.

CADM1 impairs the effect of miR-1246 on promoting cell cycle progression in chemo-resistant leukemia cells.

The interruption of normal cell cycle execution acts as an important part to the development of leukemia. It was reported that microRNAs (miRNAs) were closely related to tumorigenesis and progression, and their aberrant expression had been demonstrated to play a crucial role in numerous types of cancer. Our previous study showed that miR-1246 was preferentially overexpressed in chemo-resistant leukemia cell lines, and participated in process of cell cycle progression and multidrug resistant regulation. However, the underlying mechanism remains unclear. In present study, bioinformatics prediction and dual luciferase reporter assay indicated that CADM1 was a direct target of miR-1246. Evidently decreased expression of CADM1 was observed in relapsed primary leukemia patients and chemo-resistant cell lines. Our results furtherly proved that inhibition of miR-1246 could significantly enhance drug sensitivity to Adriamycin (ADM), induce cell cycle arrest at G0/G1 phase, promote cell apoptosis, and relieve its suppression on CADM1 in K562/ADM and HL-60/RS cells. Interference with CADM1 could reduce the increased drug sensitivity induced by miR-1246 inhibition, and notably restore drug resistance by promoting cell cycle progression and cell survival via regulating CDKs/Cyclins complexes in chemo-resistant leukemia cells. Above all, our results demonstrated that CADM1 attenuated the role of miR-1246 in promoting cell cycle progression and cell survival, thus influencing multidrug resistance within chemo-resistant leukemia cells via CDKs/Cyclins. Higher expression of miR-1246 and lower expression of CADM1 might be risk factors for leukemia.

Galectin-9 in synergy with NF-κB inhibition restores immune regulatory capability in dendritic cells of subjects with food allergy.

The pathogenesis of immune tolerance disruption is not fully understood. Galectin-9 (Gal9) has immune regulatory functions. The objective of the present study is to assess the role of Gal9 in maintaining immune tolerance. Blood and intestinal biopsies were taken from patients with food allergy (FA). The status of tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cells) in the samples was evaluated and used as representative parameters of immune tolerance. An FA mouse model was established to assess the role of Gal9 in maintaining immune tolerance. We found that peripheral CD11c+ CD5+ CD1d+ tDC frequency was significantly lower in FA patients as compared to health control (HC) subjects. There was no significant change in CD11c+ DC frequency between the FA group and the HC group. The expression of IL-10 in peripheral tDCs was lower in the FA group than that in the HC group. A positive correlation was detected between the serum levels of IL-10 and Gal9. The expression of Gal9 was observed in intestinal biopsies, which was positively correlated with the serum levels of Gal9 as well as serum IL-10 levels. Peripheral Tr1 cells had lower frequencies in the FA group than in the non-FA (Con) group. tDCs demonstrated the ability to generate Tr1 cells, which was weaker in the FA group as compared with the Con group. Exposure of FA tDCs to Gal9 in culture restored the ability to generate Tr1 cells. In summary, the lower frequency of tDC and Tr1 cell of FA patients was associated with the levels of Gal9. The presence of Gal9 restored the capacity of tDC to generate Tr1 cells.

MicroRNA-5195-3p mediated malignant biological behaviour of insulin-resistant liver cancer cells via SOX9 and TPM4.

BACKGROUND: Primary liver cancer is a malignant tumour of the digestive system, ranking second in cancer mortality in China. In different types of cancer, such as liver cancer, microRNAs (miRNAs) have been shown to be dysregulated. However, little is known about the role of miR-5195-3p in insulin-resistant liver cancer. METHODS AND RESULTS: In this study, in vitro and in vivo experiments were conducted to identify the altered biological behaviour of insulin-resistant hepatoma cells (HepG2/IR), and we proved that HepG2/IR cells had stronger malignant biological behaviour. Functional experiments showed that enhanced expression of miR-5195-3p could inhibit the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and chemoresistance of HepG2/IR cells, while impaired expression of miR-5195-3p in HepG2 cells resulted in the opposite effects. Bioinformatics prediction and dual luciferase reporter gene assays proved that SOX9 and TPM4 were the target genes of miR-5195-3p in hepatoma cells. CONCLUSIONS: In conclusion, our study demonstrated that miR-5195-3p plays a critical role in insulin-resistant hepatoma cells and might be a potential therapeutic target for liver cancer.

Culturing partial-denitrification (PD) granules in continuous flow reactor with waste sludge as inoculum: performance, granular sludge characteristics and microbial community.

Partial denitrification granular sludge (PDGS) can provide long-term stable nitrite for anaerobic ammonia oxidation (anammox). The cultivation of ordinary activated sludge from wastewater treatment plants into PDGS can further promote the application of PD in practical engineering. In this study, the feasibility of fast start-up of PDGS was explored by inoculating waste sludge in up-flow anaerobic sludge blanket (UASB) reactor with synergistic control of nitrogen load rate (NLR, 0.05-0.65 kg N/m3/d) and electron donor starvation (EDS) (240-168 mg L-1), and system performance, particle characteristics and microbial structure were studied. The results showed that PD-UASB started successfully within 48 days, the average nitrite accumulation rate (NTR) and nitrate removal ratio (NRR) reached 79.6% and 82.5% after successful initiation, accompanied by high abundance of PD bacteria (Thauera, Pseudomonas, unclassflied commamonadaceae and Limnobacter) (25.3%). The increase of PD activity, and the difference between nitrate reductase (NAR) and nitrite reductase (NIR) contributed to nitrite production. Besides, the sludge shifted from flocculated (≤0.5 mm, 95.37%) to granulated state (0.5-2 mm, 64.74%), which could be due to the increase of extracellular polymers (EPS) (especially T-EPS) and metabolism of specific microorganisms (Bacteroidota and Chloroflexi, 19.92%). Good sludge granulation promoted the settleability of PD (the SVI5 was 47.248 mL/ g. ss after successful start-up). In summary, good PD sludge granulation process could be achieved in a short time by synergistically controlling NLR and EDS.

A facile synthesis of K3PMo12O40/WO3 crystals for effective sonocatalytic performance.

Proper treatment of hazardous contaminants in the air, land, and water is crucial to environmental remediation. Sonocatalysis, by using ultrasound and suitable catalysts, has shown its potential in organic pollutant removal. In this work, K3PMo12O40/WO3 sonocatalysts were fabricated via a facile solution method at room temperature. Techniques such as powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy, and X-ray photoelectron spectroscopy were used to characterize the structure and morphology of the products. By using the K3PMo12O40/WO3 sonocatalyst, an ultrasound-assisted advanced oxidation process has been developed for the catalytic degradation of methyl orange and acid red 88. Almost all dyes were degraded within 120 min of ultrasound baths, proving that the K3PMo12O40/WO3 sonocatalyst has the advantage of speeding up the decomposition of contaminants. The impacts of key parameters, including catalyst dosage, dye concentration, dye pH, and ultrasonic power were evaluated to understand and reach optimized conditions in sonocatalysis. The remarkable performance of K3PMo12O40/WO3 in the sonocatalytic degradation of pollutants provides a new strategy for the application of K3PMo12O40 in sonocatalysis.

Integrating Relational Knowledge With Text Sequences for Script Event Prediction.

Script event prediction aims to infer subsequent events given an incomplete script. It requires a deep understanding of events, and can provide support for a variety of tasks. Existing models rarely consider the relational knowledge between events, they regard scripts as sequences or graphs, which cannot capture the relational information between events and the semantic information of script sequences jointly. To address this issue, we propose a new script form, relational event chain, that combines event chains and relational graphs. We also introduce a new model, relational-transformer, to learn embeddings based on this new script form. In particular, we first extract the relationship between events from an event knowledge graph to formalize scripts as relational event chains, then use the relational-transformer to calculate the likelihood of different candidate events, where the model learns event embeddings that encode both semantic and relational knowledge by combining transformers and graph neural networks (GNNs). Experimental results on both one-step inference and multistep inference tasks show that our model can outperform existing baselines, indicating the validity of encoding relational knowledge into event embeddings. The influence of using different model structures and different types of relational knowledge is analyzed as well.

Social work research ethics in China: A scoping review of research involving human subjects during COVID-19.

As the first review to systematically explore the scope and application of Chinese social work research ethics, this study incorporated web-crawling technology in the scoping review process and identified 18 eligible studies from 1168 publications from January 2020 to July 2021. Findings suggest that social work scholars are aware of research ethics when conducting human subjects research in the Chinese population. Yet, many failed to fully demonstrate practical considerations of internationally accepted ethical principles (e.g. respect for persons). We discuss education on research ethics, new challenges of the digital age, and considerations of Chinese culture in developing ethical protocols for social work research in China.

Anti-tumor effects of P-LPK-CPT, a peptide-camptothecin conjugate, in colorectal cancer.

To explore highly selective targeting molecules of colorectal cancer (CRC) is a challenge. We previously identified a twelve-amino acid peptide (LPKTVSSDMSLN, namely P-LPK) by phage display technique which may specifically binds to CRC cells. Here we show that P-LPK selectively bind to a panel of human CRC cell lines and CRC tissues. In vivo, Gallium-68 (68Ga) labeled P-LPK exhibits selective accumulation at tumor sites. Then, we designed a peptide-conjugated drug comprising P-LPK and camptothecin (CPT) (namely P-LPK-CPT), and found P-LPK-CPT significantly inhibits tumor growth with fewer side effects in vitro and in vivo. Furthermore, through co-immunoprecipitation and molecular docking experiment, the glutamine transporter solute carrier 1 family member 5 (SLC1A5) was identified as the possible target of P-LPK. The binding ability of P-LPK and SLC1A5 is verified by surface plasmon resonance and immunofluorescence. Taken together, P-LPK-CPT is highly effective for CRC and deserves further development as a promising anti-tumor therapeutic for CRC, especially SLC1A5-high expression type.

SF6 High-Voltage Circuit Breaker Contact Status Detection at Different Currents.

Currently, the online non-destructive testing (NDT) methods to measure the contact states of high-voltage circuit breakers (HVCBs) with SF6 gas as a quenching medium are lacking. This paper aims to put forward a novel method to detect the contact state of an HVCB based on the vibrational signal. First, for a 40.5-kV SF6 HVCB prototype, a mechanical vibration detection system along with a high-current generator to provide the test current is designed. Given this, vibration test experiments are carried out, and the vibration signal data under various currents and corresponding contact states are obtained. Afterward, a feature extraction method based on the frequency is designed. The state of the HVCB contacts is then determined using optimized deep neural networks (DNNs) along with the method of adaptive moment estimation (Adam) on the obtained experimental data. Finally, the hyperparameters for the DNNs are tuned using the Bayesian optimization (BO) technique, and a global HVCB contact state recognition model at various currents is proposed. The obtained results clearly depict that the proposed recognition model can accurately identify five various contact states of HVCBs for the currents between 1000 A and 3500 A, and the recognition accuracy rate is above 96%. The designed experimental and theoretical analysis in our study will provide the references for future monitoring and diagnosis of faults in HVCBs.

iTRAQ-Based Proteome Profiling of Differentially Expressed Proteins in Insulin-Resistant Human Hepatocellular Carcinoma.

Recently, the incidences of insulin resistance (IR) and IR-related complications have increased throughout the world, which also associate with poor prognosis in hepatocellular carcinoma (HCC). Numerous studies had been focused on the role of IR in tumorigenesis and prognosis of HCC. The proteomic analysis of IR related hepatocellular carcinoma had not been reported by now. In the present study, 196 differentially expressed proteins (DEPs) were identified between insulin resistant HepG2 cells and their parental cells, of which 109 proteins were downregulated and 87 proteins were upregulated. Bioinformatics analysis indicated that these DEPs were highly enriched in process of tumorigenesis and tumor progression. PPI network analysis showed that SOX9, YAP1 and GSK3ß as the key nodes, were involved in Wnt and Hippo signaling pathways. Survival analysis revealed that high expression of SOX9 and PRKD3 were strongly associated with reduced patient survival rate. parallel reaction monitoring (PRM) and Western blot analysis were applied to verify the protein level of these four key nodes mentioned above, which showed the same trend as quantified by isobaric tags for relative and absolute quantitation (iTRAQ) and confirmed the reliability of our Proteome Profiling analysis. Our results indicated that IR related dysregulation of protein expression might participated in tumorigenesis and malignant phenotype of hepatocarcinoma cells.

Integrated Traditional Chinese Medicine Improves Functional Outcome in Acute Ischemic Stroke: From Clinic to Mechanism Exploration With Gut Microbiota.

As a life-threatening disease, stroke is the leading cause of death and also induces adult disability worldwide. To investigate the efficacy of the integrated traditional Chinese medicine (ITCM) on the therapeutic effects of acute ischemic stroke (AIS) patients, we enrolled 26 patients in the ITCM [Tanhuo decoction (THD) + Western medicine (WM)] group and 23 in the WM group. Thirty healthy people were also included in the healthy control (HC) group. ITCM achieved better functional outcomes than WM, including significant reduction of the phlegm-heat syndrome and neurological impairment, and improvement of ability. These facts were observed in different pretreatment gut enterotypes. In this paper, we collected the stool samples of all participants and analyzed the 16S rRNA sequence data of the gut microbiota. We identified two enterotypes (Type-A and Type-B) of the gut microbial community in AIS samples before treatment. Compared to Type-B, Type-A was characterized by a high proportion of Bacteroides, relatively high diversity, and severe functional damage. In the ITCM treatment group, we observed better clinical efficacy and positive alterations in microbial diversity and beneficial bacterial abundance, and the effect of approaching healthy people's gut microbiota, regardless of gut enterotypes identified in pretreatment. Furthermore, we detected several gut microbiota as potential therapeutic targets of ITCM treatment by analyzing the correlations between bacterial abundance alterations and functional outcomes, where Dorea with the strongest correlation was known to produce anti-inflammatory metabolite and negatively linked to trimethylamine-N-oxide (TMAO), a biomarker of AIS. This study analyzed clinical and gut microbial data and revealed the possibility of a broad application independent of the enterotypes, as well as the therapeutic targets of the ITCM in treating AIS patients with phlegm-heat syndrome.

Overexpression of IL-8 and Wnt2 is associated with prognosis of gastric cancer.

INTRODUCTION: This study is to detect the expression of inflammatory factor or neutrophil-activating factor IL-8 and Wnt2 in gastric cancer (GC) and investigate the involvement of IL-8 and Wnt2 expressions in the clinicopathological indexes and prognosis. MATERIAL AND METHODS: We detected the expression of IL-8 and Wnt2 in 100 GC tissues and 40 normal gastric mucosae using immunohistochemistry. The relationships between the IL-8 and Wnt2 expression and the clinicopathological characteristics were explored. The relationship between IL-8 expression, Wnt2 expression, and prognosis of GC was analyzed by survival curve and survival regression. RESULTS: The expression of IL-8 and Wnt2 in GC tissue was 64% and 75% respectively, which was significantly higher than that in adjacent normal gastric mucosa tissues, moreover, expressions of IL-8 and Wnt2 were positively correlated. The positive rate of IL-8 and Wnt2 expressions were correlated with lymph node metastasis and TNM staging （P < 0.01, and Wnt2 was also correlated with infiltration depth (P = 0.021), but there was no difference with age, sex, and differentiation (P > 0.05). The 3-year survival analysis showed that the survival rates of IL-8- and Wnt2-positive patients were 20% and 24%, respectively, which were significantly lower than those of negative patients. Cox regression analysis showed that IL-8 and Wnt2 may be independent factors affecting the prognosis of GC. CONCLUSIONS: Our data demonstrated that the overexpression of IL-8 and Wnt2 could be isolated prognostic factors in patients with GC and, possibly, may present new targets for the treatment of GC.

Value of biomarkers in epithelial-mesenchymal transition models of liver cancer under different interventions: a meta-analysis.

Aim: A meta-analysis was conducted to evaluate the effectiveness of crucial biomarkers in HepG2 cells during epithelial-mesenchymal transformation induced by multiple interventions. Methods: PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan Fang Data and VIP databases were systematically searched from inception to 14 June 2020, by two independent reviewers. Results: A total of 58 studies were included in the meta-analysis. E-cadherin, N-cadherin and vimentin performed well under medicinal interventions. E-cadherin worked well under genetic interventions. E-cadherin and N-cadherin also performed significantly well under tumor microenvironment interventions. Under ncRNA interventions, the expression of E-cadherin significantly changed. Conclusion: Different sets of biomarkers should be selected under various interventions based on their performance.

Case Report: A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr273Met Mutation in Arginine Vasopressin Receptor 2.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary tubular dysfunction caused mainly by X-linked recessive inheritance of AVPR2 gene mutations. Pathogenic genes are a result of mutations in AVPR2 on chromosome Xq28 and in AQP2 on chromosome 12q13. The clinical manifestations of CNDI include polyuria, compensatory polydipsia, thirst, irritability, constipation, developmental delay, mental retardation, persistent decrease in the specific gravity of urine, dehydration, and electrolyte disorders (hypernatremia and hyperchloremia). Herein, we report a rare case of CNDI caused by an AVPR2 mutation in a 2-year-old Chinese boy who had sustained polyuria, polydipsia, and irritability for more than 20 months. Laboratory examinations showed no obvious abnormality in blood sodium and chloride levels but decreased urine osmolality and specific gravity. Imaging findings were also normal. However, genetic analysis revealed a C > T transition leading to T273M missense mutations in AVPR2. We provided the boy a low-sodium diet and administered oral hydrochlorothiazide and indomethacin for 1 month, after which his clinical symptoms significantly improved. This case report suggests that CNDI is characterized by pathogenic T273M missense mutations alone and expands our understanding of the pathogenesis of CNDI.

EIF5A expression and its role as a potential diagnostic biomarker in hepatocellular carcinoma.

Introduction and objectives: Eukaryotic translation initiation factor 5A (EIF5A) is a member of the identified eIF family and played an important role in cell proliferation. There are few studies about the correlation between EIF5A and hepatocellular carcinoma (HCC). Materials and methods: We evaluated the expression of the EIF5A in human HCC cell lines and tissues by western blot analysis. Immunohistochemistry analysis of EIF5A was performed on a tissue microarray including 10 normal liver samples and 90 pathological section of HCC. Receiver operating characteristic (ROC) was introduced to obtain an optimal cut-off score for EIF5A positive expression. Results: Western blot results showed that EIF5A was highly expressed in HCC cell lines and tissues. Based on ROC curve analysis, 1/10 (10.0%) of normal hepatic tissues and 67/90 (74.4%) of HCC tissues were tested positive for EIF5A expression, which indicated that EIF5A were significantly up-regulated in HCC tissues compared with normal liver tissues (χ2=17.177, P<0.001). Furthermore, expression of EIF5A was significantly correlated with histological grade (P=0.048), clinical stage (P=0.003) and pT stage (P=0.003) but not correlated with sex (P=0.617) and age (P=0.831). Conclusions: In our study, we demonstrated the expression of EIF5A is closely correlated with HCC. In consideration of its relationship with clinicopathological parameters including histological grade, clinical stage and pT stage of HCC, EIF5A could be a potential biomarker.

MicroRNA-1246 by Targeting AXIN2 and GSK-3ß Overcomes Drug Resistance and Induces Apoptosis in Chemo-resistant Leukemia Cells.

Background and objective: Chemotherapy plays an important role in the treatment of leukemia. Multidrug resistance (MDR) induced by chemotherapy always leads to treatment failure and disease recurrence. MicroRNAs (miRNAs) have been verified as crucial components in carcinogenesis, including chemo-resistance of tumor cells, which has not been fully understood. In this study, we aimed to identify the potential candidate miRNA, miR-1246, and reveal its regulatory role in chemo-resistance of leukemia cells. Methods: Candidate miRNAs were selected by microarray analysis, screened by bioinformatics tools and verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Chemo-resistant phenotypes, including cell viability, apoptosis, adriamycin (ADM) efflux and in vivo oncogenicity of leukemia cells following transfected with miR-1246 mimics or inhibitor were checked with or without ADM treatment to make clear the relationship between miR-1246 and chemo-resistance. RT-qPCR, western blot and dual luciferase reporter assay were performed to measure the expression of related genes and address the potential regulatory mechanism of miR-1246 in chemo-resistance. Results: The expression of miR-1246 was significantly higher in chemo-resistant leukemia K562/ADM cells, HL-60/RS cells and recurrent primary leukemia cells. Loss of miR-1246 inhibited proliferation, induced apoptosis, altered cell cycle distribution, inhibited ADM efflux in chemo-resistant leukemia cells, while overexpression of miR-1246 showed the opposite role in chemo-sensitive leukemia cells. Both bioinformatics prediction and luciferase assay indicated that AXIN2 and glycogen synthase kinase 3 beta (GSK-3ß) were the direct targets of miR-1246 in leukemia cells. Inhibition of miR-1246 could up-regulate AXIN2 and GSK-3ß and inactivate Wnt/ß-catenin pathway, accompanied with inhibiting the expression of ß-catenin and further influencing the expression of P-glycoprotein (P-gp) in the chemo-resistant leukemia cells. Conclusions: Chemo-resistant ability of MDR leukemia cells is attenuated by loss of miR-1246 via negatively regulating AXIN2 and GSK-3ß to inactivate Wnt/ß-catenin pathway and suppress P-gp expression, these mean that targeting miR-1246-AXIN2/GSK-3ß-Wnt/ß-catenin axis may be beneficial to overcome the chemo-resistance in relapse and refractory leukemia patients.