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1.
J Cell Mol Med ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997691

RESUMO

The overactivation of canonical Wnt/ß-catenin pathway and the maintenance of cancer stem cells (CSCs) are essential for the onset and malignant progression of most human cancers. However, their regulatory mechanism in colorectal cancer (CRC) has not yet been well demonstrated. Low-density lipoprotein receptor-related protein 5 (LRP5) has been identified as an indispensable co-receptor with frizzled family members for the canonical Wnt/ß-catenin signal transduction. Herein, we show that activation of LRP5 gene promotes CSCs-like phenotypes, including tumorigenicity and drug resistance in CRC cells, through activating the canonical Wnt/ß-catenin and IL-6/STAT3 signalling pathways. Clinically, the expression of LRP5 is upregulated in human CRC tissues and closely associated with clinical stages of patients with CRC. Further analysis showed silencing of endogenous LRP5 gene is sufficient to suppress the CSCs-like phenotypes of CRC through inhibiting these two pathways. In conclusion, our findings not only reveal a regulatory cross-talk between canonical Wnt/ß-catenin signalling pathway, IL-6/STAT3 signalling pathway and CD133-related stemness that promote the malignant behaviour of CRC, but also provide a valuable target for the diagnosis and treatment of CRC.

2.
J Exp Clin Cancer Res ; 41(1): 14, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996504

RESUMO

BACKGROUND: Chemoresistance is a main obstacle in gastric cancer (GC) treatment, but its molecular mechanism still needs to be elucidated. Here, we aim to reveal the underlying mechanisms of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resistance in GC. METHODS: We performed RNA sequencing (RNA-seq) on samples from patients who were resistant or sensitive to nab-paclitaxel, and identified Zinc Finger Protein 64 (ZFP64) as critical for nab-paclitaxel resistance in GC. CCK8, flow cytometry, TUNEL staining, sphere formation assays were performed to investigate the effects of ZFP64 in vitro, while subcutaneous tumor formation models were established in nude mice or humanized mice to evaluate the biological roles of ZFP64 in vivo. Chromatin immunoprecipitation sequencing (CHIP-seq) and double-luciferase reporter gene assay were conducted to reveal the underlying mechanism of ZFP64. RESULTS: ZFP64 overexpression was linked with aggressive phenotypes, nab-paclitaxel resistance and served as an independent prognostic factor in GC. As a transcription factor, ZFP64 directly binds to Galectin-1 (GAL-1) promoter and promoted GAL-1 transcription, thus inducing stem-cell like phenotypes and immunosuppressive microenvironment in GC. Importantly, compared to treatment with nab-paclitaxel alone, nab-paclitaxel plus GAL-1 blockade significantly enhanced the anti-tumor effect in mouse models, particularly in humanized mice. CONCLUSIONS: Our data support a pivotal role for ZFP64 in GC progression by simultaneously promoting cellular chemotherapy resistance and tumor immunosuppression. Treatment with the combination of nab-paclitaxel and a GAL-1 inhibitor might benefit a subgroup of GC patients.

3.
Exp Mol Med ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022544

RESUMO

Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family, members of which play essential roles in diverse cellular processes during carcinogenesis, including cell proliferation, differentiation, migration, and invasion. Unlike other MAPKs, ERK3 is an unstable protein with a short half-life. Although deubiquitination of ERK3 has been suggested to regulate the activity, its ubiquitination has not been described in the literature. Here, we report that FBXW7 (F-box and WD repeat domain-containing 7) acts as a ubiquitination E3 ligase for ERK3. Mammalian two-hybrid assay and immunoprecipitation results demonstrated that ERK3 is a novel binding partner of FBXW7. Furthermore, complex formation between ERK3 and the S-phase kinase-associated protein 1 (SKP1)-cullin 1-F-box protein (SCF) E3 ligase resulted in the destabilization of ERK3 via a ubiquitination-mediated proteasomal degradation pathway, and FBXW7 depletion restored ERK3 protein levels by inhibiting this ubiquitination. The interaction between ERK3 and FBXW7 was driven by binding between the C34D of ERK3, especially at Thr417 and Thr421, and the WD40 domain of FBXW7. A double mutant of ERK3 (Thr417 and Thr421 to alanine) abrogated FBXW7-mediated ubiquitination. Importantly, ERK3 knockdown inhibited the proliferation of lung cancer cells by regulating the G1/S-phase transition of the cell cycle. These results show that FBXW7-mediated ERK3 destabilization suppresses lung cancer cell proliferation in vitro.

4.
Int J Pharm ; 615: 121480, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35041917

RESUMO

Paeoniflorin (PF) has a certain therapeutic effect on cholestasis liver injury. To further improve the bioavailability of PF and play its pharmacological role in liver protection, PF-phospholipid complex micelles (PF-PLC micelles) were prepared based on our previous research on PF-PLC. The protective effects of PF and PF-PLC micelles on cholestasis liver injury induced by 17α-ethynylestradiol (EE) were compared, and the possible mechanisms were further explored. Herein, we showed that PF-PLC micelles effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. Mechanism studies indicated that PF-PLC micelles treatment could suppress the TLR4/MyD88/NF-κB pathway, and further reduce the levels of pro-inflammatory factors. Meanwhile, our experimental results demonstrated that the beneficial effect of PF-PLC micelles on EE-induced cholestasis may be achieved by the upregulation of nuclear receptors and metabolic enzymes (PXR/CAR/UGT1A1). All these results indicate that PF-PLC micelles have great potential in the treatment of cholestatic liver disease.

5.
Am J Clin Pathol ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34871348

RESUMO

OBJECTIVES: We aimed to evaluate the effects of hemoglobin (Hb) variants prevalent in China on HbA1c measurements and to identify them during HbA1c measurements. METHODS: We evaluated a cation-exchange high-performance liquid chromatography (HPLC) method (Bio-Rad D-100), a capillary electrophoresis (CE) method (Capillarys 3 TERA), an immunoassay (Cobas c501), and a boronate affinity method (Premier Hb9210, as a comparative method) for HbA1c measurements in the presence of Hb variants prevalent in China. RESULTS: The Bio-Rad D-100 and Capillarys 3 TERA gave specific retention times and numeric migration positions for each Hb variant, respectively, showing excellent interindividual reproducibility. All methods showed statistically significant differences (P < .01) for several variants. Clinically significant effects were observed for the Bio-Rad D-100 (Hb New York and Hb J-Bangkok), Capillarys 3 TERA (Hb New York and Hb J-Bangkok), and Cobas c501 (Hb New York). Among 297 samples with Hb variants, there were 75 (25.3%) unacceptable results for Bio-Rad D-100, 28 (9.4%) for Capillarys 3 TERA, and 19 (6.4%) for Cobas c501 compared with the results from Premier Hb9210. CONCLUSIONS: Some Hb variants prevalent in China affect HbA1c measurements. The HPLC retention time and CE migration position can aid in the presumptive identification of Hb variants.

6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 1047-1050, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34891468

RESUMO

Local field potentials (LFPs) have better long-term stability compared with spikes in brain-machine interfaces (BMIs). Many studies have shown promising results of LFP decoding, but the high-dimensional feature of LFP still hurdle the development of the BMIs to low-cost. In this paper, we proposed a framework of a 1D convolution neural network (CNN) to reduce the dimensionality of the LFP features. For evaluating the performance of this architecture, the reduced LFP features were decoded to cursor position (Center-out task) by a Kalman filter. The Principal components analysis (PCA) was also performed as a comparison. The results showed that the CNN model could reduce the dimensionality of LFP features to a smaller size without significant performance loss. The decoding result based on the CNN features outperformed that based on the PCA features. Moreover, the reduced features by CNN also showed robustness across different sessions. These results demonstrated that the LFP features reduced by the CNN model achieved low cost without sacrificing high-performance and robustness, suggesting that this method could be used for portable BMI systems in the future.

7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 6402-6405, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34892577

RESUMO

With the development of calcium imaging, neuroscientists have been able to study neural activity with a higher spatial resolution. However, the real-time processing of calcium imaging is still a big challenge for future experiments and applications. Most neuroscientists have to process their imaging data offline due to the time-consuming of most existing calcium imaging analysis methods. We proposed a novel online neural signal processing framework for calcium imaging and established an Optical Brain-Computer Interface System (OBCIs) for decoding neural signals in real-time. We tested and evaluated this system by classifying the calcium signals obtained from the primary motor cortex of mice when the mice were performing a lever-pressing task. The performance of our online system could achieve above 80% in the average decoding accuracy. Our preliminary results show that the online neural processing framework could be applied to future closed-loop OBCIs studies.

8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 6445-6448, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34892587

RESUMO

In the research of motion control using brain-machine interface (BMI), analysis is usually conducted on one ensemble of neurons whose activity serves as direct input to the BMI decoder (control units). The number of control units is diverse in different control modes. That is to say, the size of dimensions of neural signals used in motion control is diverse. However, how will the behavioral performance change with this kind of diversity? What effects does this diversity have on modulation characteristics of control units? To answer these questions, we designed three modes of motion tasks using neural signals with different dimension sizes to control. Our results imply that as the dimension reduces, some deviations appear in behavioral performance. At the same time, the control units tend to have a directional division of control, then enhance their stability and increase modulations after division.

9.
Zhongguo Zhong Yao Za Zhi ; 46(21): 5496-5511, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951201

RESUMO

Salviae Miltiorrhizae Radix et Rhizoma is a Chinese herbal medicine that promotes blood circulation to remove blood stasis, nourishes blood to tranquilize the mind, and cools blood to disperse carbuncles. Salviae Miltiorrhizae Radix et Rhizoma has microcirculation-improving, blood vessel-dilating, atherosclerosis-preventing, anti-inflammatory, anti-tumor, and blood pressure-and blood lipid-lowering activities. As research progresses, the chemical composition, pharmacological effect, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma have attracted much attention. We reviewed the research progress in this field. Based on the concept of quality marker(Q-marker) in traditional Chinese medicine, the Q-markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted and analyzed from the aspects of quality transfer, traceability, ingredient specificity, association between ingredients and pharmacological effects, ingredient predictability, and compounding environment. This review provides a scientific basis for the quality control of Salviae Miltiorrhizae Radix et Rhizoma and its preparations.


Assuntos
Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Raízes de Plantas , Rizoma
10.
Zhongguo Zhong Yao Za Zhi ; 46(21): 5512-5521, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951202

RESUMO

Zhenwu Decoction(ZWD) has a history of more than 1 800 years in traditional Chinese medicine(TCM), which is used to treat various diseases characterized by Yangqi deficiency and exuberant water and dampness. It is currently the classic prescription for the treatment of chronic heart failure(CHF). This study provides a basis for the treatment of CHF with ZWD by elaborating the traditional efficacy, theoretical basis, and underlying mechanism of the prescription. Based on the research methods and judgment basis of quality markers(Q-markers) of Chinese medicine, the Q-markers of ZWD in the treatment of CHF were predicted from the aspects of transfer and traceability, specificity, effectiveness, compatibility environment, measurability, and processing. Demethyl-coclaurine,benzoylaconine, atractylenolide Ⅲ, paeoniflorin, 6-gingerol, 8-gingerol, pachymic acid, and dehydrotumulosic acid can be used as Q-markers of ZWD for treating CHF. The result provides a reference for exploring the pharmacodynamic substances of ZWD in the treatment of CHF.


Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Biomarcadores , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa
11.
Front Cell Dev Biol ; 9: 760980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901005

RESUMO

Atherosclerosis is a chronic inflammation of the arterial vessel wall driven by lipid metabolism disorders. Although helminthic infection and their derivatives have been identified to attenuate the chronic inflammatory diseases, the immunomodulatory effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) on metabolic diseases and atherosclerosis has not been reported. In this study, we investigated the therapeutic efficacy of rSj-Cys on atherosclerotic renal damage and explored the related immunological mechanism. The results demonstrated that treatment with rSj-Cys significantly reduced body weight gain, hyperlipidemia, and atherosclerosis induced by the high-fat diet in apoE-/- mice. The treatment of rSj-Cys also significantly improved kidney functions through promoting macrophage polarization from M1 to M2, therefore inhibiting M1 macrophage-induced inflammation. The possible mechanism underlying the regulatory effect of rSj-Cys on reducing atherosclerosis and atherosclerotic renal damage is that rSj-Cys stimulates regulatory T cell and M2 macrophage polarization that produce regulatory cytokines, such as interleukin 10 and transforming growth factor ß. The therapeutic effect of rSj-Cys on atherosclerotic renal damage is possibly through inhibiting the activation of TLR2/Myd88 signaling pathway. The results in this study provide evidence for the first time that Schistosoma-derived cystatin could be developed as a therapeutic agent to treat lipid metabolism disorder and atherosclerosis that threats million lives around the world.

12.
Am J Pathol ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34896072

RESUMO

The overactivation of canonical Wnt/ß-catenin pathway is one of the main cascades for the initiation, progression, and recurrence of most human malignancies. As an indispensable coreceptor for the signaling transduction of the canonical Wnt/ß-catenin pathway, LRP5 is up-regulated and exerts a carcinogenic role in most types of cancer. However, its expression level and role in gastric cancer (GC) has not been clearly elucidated. The current work showed that LRP5 was overexpressed in GC tissues and the expression of LRP5 was positively associated with the advanced clinical stages and poor prognosis. Ectopic expression of LRP5 enhanced the proliferation, invasiveness, and drug resistance of GC cells in vitro, and accelerated the tumor growth in nude mice, through activating the canonical Wnt/ß-catenin signaling pathway and up-regulating aerobic glycolysis, thus increasing the energy supply for GC cells. Additionally, the expression of LRP5 and glycolysis-related genes showed an obviously positive correlation in GC tissues. By contrast, the exact opposite results were observed when the endogenous LRP5 was silenced in GC cells. Collectively, these results not only reveal the carcinogenic role of LRP5 during GC development through activating the canonical Wnt/ß-catenin and glycolysis pathways, but also provide a valuable candidate for the diagnosis and treatment of human GC.

13.
Mol Med ; 27(1): 144, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740314

RESUMO

BACKGROUND: The gut microbiome is the totality of microorganisms, bacteria, viruses, protozoa, and fungi within the gastrointestinal tract. The gut microbiome plays key roles in various physiological and pathological processes through regulating varieties of metabolic factors such as short-chain fatty acids, bile acids and amino acids. Nuclear receptors, as metabolic mediators, act as a series of intermediates between the microbiome and the host and help the microbiome regulate diverse processes in the host. Recently, nuclear receptors such as farnesoid X receptor, peroxisome proliferator-activated receptors, aryl hydrocarbon receptor and vitamin D receptor have been identified as key regulators of the microbiome-host crosstalk. These nuclear receptors regulate metabolic processes, immune activity, autophagy, non-alcoholic and alcoholic fatty liver disease, inflammatory bowel disease, cancer, obesity, and type-2 diabetes. CONCLUSION: In this review, we have summarized the functions of the nuclear receptors in the gut microbiome-host axis in different physiological and pathological conditions, indicating that the nuclear receptors may be the good targets for treatment of different diseases through the crosstalk with the gut microbiome.

14.
Clin Cancer Res ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740924

RESUMO

PURPOSE: Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many "cold" tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy. EXPERIMENTAL DESIGN: Analysis of transcriptomic profiles at single-cell resolution was performed in clinical patients' samples, along with integrated analysis of multiple RNA-seq datasets. The antitumor activity of YY001, a novel EP4 antagonist, combined with anti-programmed cell death protein 1 (PD-1) antibody was evaluated both in vitro and in vivo Results: We identified EP4 (PTGER4) as expressed in epithelial cells and various immune cells and involved in modulating the prostate cancer immune microenvironment. YY001, a novel EP4 antagonist, inhibited the differentiation, maturation, and immunosuppressive function of myeloid-derived suppressor cells (MDSCs) while enhancing the proliferation and anticancer functions of T cells. Furthermore, it reversed the infiltration levels of MDSCs and T cells in the tumor microenvironment by overturning the chemokine profile of tumor cells in vitro and in vivo The combined immunotherapy demonstrated a robust antitumor immune response as indicated by the robust accumulation and activation of CD8+ cytotoxic T cells, with a significantly decreased MDSC ratio and reduced MDSC immunosuppression function. CONCLUSIONS: Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti-PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory.

15.
J Pediatr Orthop B ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34723915

RESUMO

The aim of this study was to evaluate the characteristics of paediatric hand fractures (PHF) at a tertiary hospital in South China based on sex, age, mechanism of injury and anatomical region. A retrospective observational study was performed on children aged 15 years and younger who were referred for actual or suspected hand fractures between January 2016 and December 2020. Medical records and radiographs were reviewed for age at the time of injury, sex, site and fracture pattern and mechanism of injury. A total of 436 consecutive children with 478 hand fractures were reviewed. Hand fractures was more common in boys (281/436; 64.4%) than in girls (155/436; 35.6%), although most fractures occurred in children aged 0-3 years (198/436; 45.4%). Distal phalanges were the most commonly injured bones (184/478; 38.5%), and the base fractures were most common (151/476; 31.7%); the fifth digit was most commonly injured (150/478; 31.3%). Crush injuries were the leading cause of fracture in children younger than 6 years of age (207/325; 63.7%), whereas punch injuries were the major cause of injury in older age groups (55/153; 35.9%); 60.1% of the fractures were managed nonsurgically. This study showed patterns of PHF in a tertiary hospital in South China. It illustrates the local variability across sex, age group, injury type and injury mechanism. Such demographic data will be valuable for optimally resourcing healthcare systems locally and help guide prevention policies.

16.
Arch Virol ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34826002

RESUMO

A novel positive single-stranded RNA virus, Sclerotinia sclerotiorum hypovirus 9 (SsHV9), was identified in the plant-pathogenic Sclerotinia sclerotiorum strain GB375, which was associated with a garden bean plant in the United States. The complete genome of SsHV9 is 14,067 nucleotides in length, excluding the poly(A) tail. It has a single large open reading frame encoding a putative polyprotein (4,196 amino acids), which is predicted to contain a papain-like protease, a protein of unknown function, an RNA-dependent RNA polymerase, and an RNA helicase. Phylogenetic analysis based on a multiple alignment of amino acid sequences of polyproteins that suggested SsHV9 belongs to the proposed genus "Alphahypovirus" in the family Hypoviridae.

17.
Anal Chem ; 93(46): 15468-15473, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34766749

RESUMO

A laser frequency-locked hollow waveguide (HWG) gas sensor is demonstrated for simultaneous measurements of three isotopologues (12CO2, 13CO2, and 18OC16O) using wavelength modulation spectroscopy with a 2.73 µm distributed feedback laser. The first harmonic (1f) signal at the sampling point where the peak of the second harmonic (2f) signal was located was employed as the locking point to lock the laser frequency to the transition center of 13CO2, while the absorption lines of 12CO2 and 18OC16O were being scanned. Continuous measurements of the three isotopologues of 4.7% CO2 samples over 103 min under free running and frequency locking conditions were performed. The measurement accuracy and precision of the three isotopologues achieved under the frequency locking condition were at least 3 times and 1.3 times better than those obtained under the free running condition, respectively. The Allan variance plot of the developed laser-locked HWG gas sensor shows a detection limit of 0.72‰ for both δ13C and δ18O under the frequency locking condition with a long stability time of 766 s. This study demonstrated the high potential of a novel human breath diagnostic sensor for medical diagnostic with high accuracy, precision, and sensitivity and without frequently repeated calibration.


Assuntos
Dióxido de Carbono , Lasers , Humanos , Análise Espectral
18.
Opt Express ; 29(24): 40323-40332, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809376

RESUMO

Sub-100 fs pulse generation from a passively mode-locked Tm,Ho-codoped cubic multicomponent disordered garnet laser at ∼2 µm is demonstrated. A single-walled carbon nanotube saturable absorber is implemented to initiate and stabilize the soliton mode-locking. The Tm,Ho:LCLNGG (lanthanum calcium lithium niobium gallium garnet) laser generated pulses as short as 63 fs at a central wavelength of 2072.7 nm with an average output power of 63 mW at a pulse repetition rate of ∼102.5 MHz. Higher average output power of 121 mW was obtained at the expense of longer pulse duration (96 fs) at 2067.6 nm using higher output coupling. To the best of our knowledge, this is the first report on mode-locked operation of the Tm,Ho:LCLNGG crystal.

19.
Cells ; 10(11)2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34831031

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available. Bile acids (BAs) are not only important physiological detergents for the absorption of lipid-soluble nutrients in the intestine but also metabolic regulators. During the last two decades, BAs have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis has been associated with NAFLD disease severity. Identification of nuclear receptors and G-protein-coupled receptors activated by different BAs not only significantly expanded the current understanding of NAFLD/NASH disease progression but also provided the opportunity to develop potential therapeutics for NAFLD/NASH. In this review, we will summarize the recent studies with a focus on BA-mediated signaling pathways in NAFLD/NASH. Furthermore, the therapeutic implications of targeting BA-mediated signaling pathways for NAFLD will also be discussed.

20.
Cancer Manag Res ; 13: 8025-8035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712060

RESUMO

Background: The dysregulation of microRNAs (miRNAs) and hepatotoxicity due to the aberrant accumulation of bile acids (BAs) are notorious causes that predispose an individual to the development of hepatocellular carcinoma (HCC). Farnesoid X receptor (FXR), encoded by NR1H4 gene, has been identified as a crucial BA receptor to maintain the homeostasis of BA pool and its expression is decreased in HCC. miR-382-5p plays an important role in the pathogenesis of many human malignancies and was reported to promote the proliferation and differentiation of normal liver cells and liver regeneration. However, there is still some controversy about its role in HCC microenvironment. This study aims to explore the expression pattern of miR-382-5p in HCC and its role in regulating FXR during the development of HCC. Methods: Tissues collected from 30 HCC patients were subjected to extraction of total RNA and quantitative real-time PCR (qRT-PCR) for the analyses of miR-382-5p expression and NR1H4 mRNA levels, and their expressions were verified by analyzing the online HCC-related GSE datasets. The role of miR-382-5p in regulating cellular proliferation and expression of FXR in different HCC cell lines was analyzed by qRT-PCR, Western Blot, real-time cellular analysis (RTCA) and luciferase reporter assays. The role of miR-382-5p in regulating downstream genes of FXR in HCC cells was also analyzed. Results: miR-382-5p was upregulated in HCC tissues and inversely associated with the downregulation of NR1H4 mRNA levels. The luciferase reporter assay proved that miR-382-5p directly targeted the 3'-untranslated region (3'-UTR) of human NR1H4 mRNA. Overexpression of miR-382-5p led to a malignant proliferation of HCC cells by suppressing the expression of FXR. In contrast, blocking the endogenous miR-382-5p was sufficient to suppress the cellular proliferation rate of HCC through increasing FXR expression. Additionally, miR-382-5p inhibited the expression of some target genes of FXR, including SHP, FGF19 and SLC51A, and this inhibitory effect was FXR-dependent. Conclusion: Therefore, miR-382-5p promotes the progression of HCC in vitro by suppressing FXR and could serve as a valuable therapeutic target for HCC treatment.

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