Abstract 525: The Role of FHL2 in Mechanically Regulated Valve Interstitial Cell Osteogenic Differentiation

Introduction: Lesions in calcific aortic valve disease (CAVD) often include osteoblasts and occur preferentially in the natively stiffer fibrosa side of the valve, suggesting roles for osteogenesis and matrix stiffness in CAVD. Valve interstitial cells (VICs) have osteogenic potential that is modulated by matrix stiffness in vitro . Osteogenesis of mesenchymal stem cells is mediated by FHL2 and modulated by matrix stiffness via RhoA. However, the connection between FHL2 and RhoA and their roles in mechanically-regulated osteogenic differentiation of VICs and CAVD have not been established. Hypothesis: Matrix stiffness regulates RhoA-dependent FHL2 expression to direct VIC osteogenesis. Methods/Results: Primary porcine aortic VICs were grown on collagen-coated polyacrylamide gels of varying elastic moduli in vitro . With increasing substrate stiffness, VICs demonstrated increased RhoA activation by ELISA and increased FHL2 nuclear translocation by immunofluorescence and western blotting. Notably, significant increases were seen on 22 kPa substrates, a stiffness unique to the disease-prone fibrosa, compared to 11 kPa substrates (p<0.05). We investigated the regulatory relationship between RhoA and FHL2 in VICs by controlling RhoA levels with adenoviruses. With constitutively active RhoA, FHL2 nuclear translocation increased (p<0.06); in contrast, with dominant negative RhoA, FHL2 nuclear translocation decreased (p<0.05). The effect of RhoA levels on stiffness-dependent FHL2 activity was verified by knocking down RhoA levels pharmacologically (C3 toxin) which abrogated stiffness-dependent FHL2 nuclear translocation. Alkaline phosphatase activity as a marker of osteogenesis was highest on substrates with fibrosa-like stiffness and was reduced by FHL2 siRNA knockdown. Conclusions: Together, these results support the hypothesis that mechanically-regulated VIC osteogenic differentiation in vitro is mediated by FHL2 operating downstream of RhoA. New insights into the mechanotransduction mechanisms that regulate VIC osteogenesis may lead to novel strategies for treating CAVD.

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MiR-144-5p, an exosomal miRNA from bone marrow-derived macrophage in type 2 diabetes, impairs bone fracture healing via targeting Smad1

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00964-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Dong Zhang ◽

Yifan Wu ◽

Zonghuan Li ◽

Hairen Chen ◽

Siyuan Huang ◽

...

Keyword(s):

Bone Marrow ◽

Fracture Healing ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Fracture Repair ◽

Osteogenic Potential ◽

Patients With Diabetes ◽

The Impact

Abstract Background Patients with diabetes have an increased risk of nonunion and delayed union of fractures. Macrophages have been shown as a key player in diabetic complications. However, it remains obscure how diabetic milieu affects macrophage-derived exosomes and its implications on osteogenic differentiation of BMSCs. In this study, we aim to define the impact of diabetic milieu on macrophage-derived exosomes, role of extracellular vesicles in intercellular communication with BMSCs, and subsequent effects on osteogenic differentiation and fracture repair. Results The osteogenic potential and the ability of fracture repair of exosomes derived from diabetic bone marrow-derived macrophages (dBMDM-exos) were revealed to be lower, as compared with non-diabetic bone marrow-derived macrophages (nBMDM-exos) in vitro and in vivo. Interestingly, miR-144-5p levels were sharply elevated in dBMDM-exos and it could be transferred into BMSCs to regulate bone regeneration by targeting Smad1. In addition, the adverse effects of dBMDM-exos on the osteogenic potential and the ability of fracture repair were reversed through the suppression of miR-144-5p inhibition in vitro and vivo. Conclusions The results demonstrated an important role of exosomal miR-144-5p in bone regeneration, offering insight into developing new strategy for the improvement of fracture healing in patients with diabetes mellitus. Graphic Abstract

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Role of Fzd6 in Regulating the Osteogenic Differentiation of Adipose-derived Stem Cells in Osteoporosis

10.21203/rs.3.rs-328417/v1 ◽

2021 ◽

Author(s):

Tianli Wu ◽

Zhihao Yao ◽

Gang Tao ◽

Fangzhi Lou ◽

Hui Tang ◽

...

Keyword(s):

Stem Cells ◽

Osteogenic Differentiation ◽

Wnt Signaling Pathway ◽

Osteogenic Potential ◽

Adipose Derived Stem Cells ◽

Alizarin Red ◽

Differentiation Potential

Abstract Objective: Although it has been demonstrated that adipose-derived stem cells (ASCs) from osteoporosis mice (OP-ASCs) exhibit impaired osteogenic differentiation potential, the molecular mechanism has not yet been elucidated. We found that Fzd6 was decreased in OP-ASCs compared with ASCs. This study investigates the effects and underlying mechanisms of Fzd6 in the osteogenic potential of OP-ASCs. Methods: Fzd6 expression in ASCs and OP-ASCs was measured by PCR gene chip. Fzd6 overexpression and silencing lentiviruses were used to evaluate the role of Fzd6 in the osteogenic differentiation of OP-ASCs. Real-time PCR (qPCR) and western blotting (WB) was performed to detect the expression of Fzd6 and bone-related molecules, including runt-related transcription factor 2 (Runx2) and osteopontin (Opn). Alizarin red staining and Alkaline phosphatase (ALP) staining was performed following osteogenic induction. Microscopic CT (Micro-CT), hematoxylin and eosin staining (H&E) staining, and Masson staining were used to assess the role of Fzd6 in osteogenic differentiation of osteoporosis (OP) mice in vivo.Results: Expression of Fzd6 was decreased significantly in OP-ASCs. Fzd6 silencing down-regulated the osteogenic ability of OP-ASCs in vitro. Overexpression of Fzd6 rescued the impaired osteogenic capacity in OP-ASCs in vitro. We obtained similar results in vivo.Conclusions: Fzd6 plays an important role in regulating the osteogenic ability of OP-ASCs both in vivo and in vitro. Overexpression of Fzd6 associated with the Wnt signaling pathway promotes the osteogenic ability of OP-ASCs, which provides new insights for the prevention and treatment of OP.

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Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

Biomedicines ◽

10.3390/biomedicines9040420 ◽

2021 ◽

Vol 9 (4) ◽

pp. 420

Author(s):

Su-Jung Hwang ◽

Ye-Seul Song ◽

Hyo-Jong Lee

Keyword(s):

Nitric Oxide ◽

Nuclear Translocation ◽

Raw 264.7 Cells ◽

Network Pharmacology ◽

Raw 264.7 ◽

Dependent Manner ◽

Bioactive Constituents

Kushen (Radix Sophorae flavescentis) is used to treat ulcerative colitis, tumors, and pruritus. Recently, phaseolin, formononetin, matrine, luteolin, and quercetin, through a network pharmacology approach, were tentatively identified as five bioactive constituents responsible for the anti-inflammatory effects of S. flavescentis. However, the role of phaseolin (one of the primary components of S. flavescentis) in the direct regulation of inflammation and inflammatory processes is not well known. In this study, the beneficial role of phaseolin against inflammation was explored in lipopolysaccharide (LPS)-induced inflammation models of RAW 264.7 macrophages and zebrafish larvae. Phaseolin inhibited LPS-mediated production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), without affecting cell viability. In addition, phaseolin suppressed pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in a dose-dependent manner. Furthermore, phaseolin reduced matrix metalloproteinase (MMP) activity as well as macrophage adhesion in vitro and the recruitment of leukocytes in vivo by downregulating Ninjurin 1 (Ninj1), an adhesion molecule. Finally, phaseolin inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB). In view of the above, our results suggest that phaseolin could be a potential therapeutic candidate for the management of inflammation.

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Combination of Human Amniotic Fluid Derived-Mesenchymal Stem Cells and Nano-hydroxyapatite Scaffold Enhances Bone Regeneration

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.730 ◽

2019 ◽

Vol 7 (17) ◽

pp. 2739-2750 ◽

Cited By ~ 1

Author(s):

Eman E. A. Mohammed ◽

Hanan Beherei ◽

Mohamed El-Zawahry ◽

Abdel Razik Farrag ◽

Naglaa Kholoussi ◽

...

Keyword(s):

Osteogenic Differentiation ◽

Bone Healing ◽

Therapeutic Potential ◽

Osteogenic Potential ◽

3D Scaffold ◽

Human Amniotic Fluid ◽

Post Transplantation ◽

Defect Site ◽

Tibia Defect

BACKGROUND: Human amniotic fluid-derived stem cells (hAF-MSCs) have a high proliferative capacity and osteogenic differentiation potential in vitro. The combination of hAF-MSCs with three-dimensional (3D) scaffold has a promising therapeutic potential in bone tissue engineering and regenerative medicine. Selection of an appropriate scaffold material has a crucial role in a cell supporting and osteoinductivity to induce new bone formation in vivo. AIM: This study aimed to investigate and evaluate the osteogenic potential of the 2nd-trimester hAF-MSCs in combination with the 3D scaffold, 30% Nano-hydroxyapatite chitosan, as a therapeutic application for bone healing in the induced tibia defect in the rabbit. SUBJECT AND METHODS: hAF-MSCs proliferation and culture expansion was done in vitro, and osteogenic differentiation characterisation was performed by Alizarin Red staining after 14 & 28 days. Expression of the surface markers of hAF-MSCs was assessed using Flow Cytometer with the following fluorescein-labelled antibodies: CD34-PE, CD73-APC, CD90-FITC, and HLA-DR-FITC. Ten rabbits were used as an animal model with an induced defect in the tibia to evaluate the therapeutic potential of osteogenic differentiation of hAF-MSCs seeded on 3D scaffold, 30% Nano-hydroxyapatite chitosan. The osteogenic differentiated hAF-MSCs/scaffold composite system applied and fitted in the defect region and non-seeded scaffold was used as control. The histopathological investigation was performed at 2, 3, & 4 weak post-transplantation and scanning electron microscope (SEM) was assessed at 2 & 4 weeks post-transplantation to evaluate the bone healing potential in the rabbit tibia defect. RESULTS: Culture and expansion of 2nd-trimester hAF-MSCs presented high proliferative and osteogenic potential in vitro. Histopathological examination for the transplanted hAF-MSCs seeded on the 3D scaffold, 30% Nano-hydroxyapatite chitosan, demonstrated new bone formation in the defect site at 2 & 3 weeks post-transplantation as compared to the control (non-seeded scaffold). Interestingly, the scaffold accelerated the osteogenic differentiation of AF-MSCs and showed complete bone healing of the defect site as compared to the control (non-seeded scaffold) at 4 weeks post-transplantation. Furthermore, the SEM analysis confirmed these findings. CONCLUSION: The combination of the 2nd-trimester hAF-MSCs and 3D scaffold, 30% Nano-hydroxyapatite chitosan, have a therapeutic perspective for large bone defect and could be used effectively in bone tissue engineering and regenerative medicine.

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Dominant Negative Dimerization of a Mutant Homeodomain Protein in Axenfeld-Rieger Syndrome

Molecular and Cellular Biology ◽

10.1128/mcb.23.6.1968-1982.2003 ◽

2003 ◽

Vol 23 (6) ◽

pp. 1968-1982 ◽

Cited By ~ 21

Author(s):

Irfan Saadi ◽

Adisa Kuburas ◽

Jamison J. Engle ◽

Andrew F. Russo

Keyword(s):

Dominant Negative ◽

Hill Coefficient ◽

Homeodomain Protein ◽

Yeast Two Hybrid ◽

Autosomal Dominant Disorder ◽

Rieger Syndrome ◽

A Charge ◽

Two Hybrid

ABSTRACT Axenfeld-Rieger syndrome is an autosomal-dominant disorder caused by mutations in the PITX2 homeodomain protein. We have studied the mechanism underlying the dominant negative K88E mutation, which occurs at position 50 of the homeodomain. By using yeast two-hybrid and in vitro pulldown assays, we have documented that PITX2a can form homodimers in the absence of DNA. Moreover, the K88E mutant had even stronger dimerization ability, primarily due to interactions involving the C-terminal region. Dimerization allowed cooperative binding of wild-type (WT) PITX2a to DNA containing tandem bicoid sites in a head-to-tail orientation (Hill coefficient, 1.73). In contrast, the WT-K88E heterodimer bound the tandem sites with greatly reduced cooperativity and decreased transactivation activity. To further explore the role of position 50 in PITX2a dimerization, we introduced a charge-conservative mutation of lysine to arginine (K88R). The K88R protein had greatly reduced binding to a TAATCC element and did not specifically bind any other TAATNN motif. Like K88E, K88R formed relatively stronger dimers with WT. As predicted by our model, the K88R protein acted in a dominant negative manner to suppress WT PITX2a activity. These results suggest that the position 50 residue in the PITX2 homeodomain plays an important role in both DNA binding and dimerization activities.

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Abstract 5278: The Sonic Hedgehog Transcription Factor Gli3 Modulates Ischemia-induced Angiogenesis

Circulation ◽

10.1161/circ.118.suppl_18.s_518-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Marie-Ange Renault ◽

Jerome Roncalli ◽

Joern Tongers ◽

Sol Misener ◽

Tina Thorne ◽

...

Keyword(s):

Transcription Factor ◽

Limb Ischemia ◽

Capillary Density ◽

Left Ventricular ◽

Dominant Negative ◽

Tube Length ◽

Reduced Ejection Fraction ◽

Border Zones

Gli transcription factors are mediators of hedgehog signaling and have been shown to be critical in several steps during development. We have shown that the Hedgehog pathway is reactivated in the adult cardiovascular system under ischemic conditions, however the specific role of Gli3 has not been elucidated. Adenoviral mediated overexpression of Gli3 promotes HUVEC migration (250±58% of control, p<0.001) while down regulation of Gli3 via siRNA delayed tube formation on Matrigel (total tube length after 8 hours 6.86 vs. 70.76 control), suggesting a possible role of Gli3 in angiogenesis. We next investigated the role of Gli3 in angiogenesis using Gli3 +/− (Gli3 +/XtJ ) mice, a well established model of reduced Gli3 expression. VEGF-induced corneal angiogenesis was impaired in Gli3 +/− mice compared to WT. The role of Gli3 in angiogenesis was then confirmed in two ischemia models. Hind-limb ischemia (HLI) was induced by resection of the left femoral artery. Capillary density was reduced by a mean of 48.40±12.08% in Gli3 +/− mice vs. WT 7, 14 and 28 days. Myocardial infarction (MI) was induced by ligation of the LAD. 28 days after MI, left ventricular function assessed by echo and histological analysis revealed that Gli3 +/− mice exhibit reduced ejection fraction (27.92±4.49% versus 37.56±7.02% for the WT, p=0.004), increased fibrosis area (33.65±9.73% versus 19.81±5.40% for the WT, p=0.007) and a decrease capillary density in the ischemic and border zones. These data indicate that Gli3 deficiency leads to impaired angiogenesis in both ischemic and non ischemic conditions. Moreover, the impairment in ischemia induced neovascularization is associated with more severe impairment of cardiac function after MI. The mechanism of Gli3’s effects was then investigated in vitro . Promoter reporter assays revealed that Gli3 overexpression inhibits Gli-dependent transcription, while Western analysis show increased Akt phosphorylation, activation of the ERK1/2 and increased c-Fos expression. Using a dominant negative Akt expressing virus and a MEK1/2 inhibitor, we show that Gli3 induced-EC migration is dependent on Akt and ERK1/2. These studies provide the first evidence that the Gli3 transcription factor regulates angiogenesis and EC phenotype.

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LRP8 activates STAT3 to induce PD-L1 expression in osteosarcoma

Tumori Journal ◽

10.1177/0300891620952872 ◽

2020 ◽

pp. 030089162095287

Author(s):

Shiqin Zheng ◽

Yuxi Wei ◽

Yu Jiang ◽

Yi Hao

Keyword(s):

Cell Line ◽

Culture System ◽

Nuclear Translocation ◽

Interleukin 2 ◽

Dominant Negative ◽

Jurkat Cells ◽

Osteosarcoma Cell Line ◽

Osteosarcoma Cell ◽

Normal Tissues

Purpose: Targeting programmed death-ligand 1 (PD-L1) may be an effective intervention for osteosarcoma and PD-L1 expression is controlled by diverse regulatory factors. Low-density lipoprotein receptor-related protein 8 (LRP8) regulates osteoblast differentiation and it is unclear whether and how LRP8 could contribute to osteosarcoma pathogenesis. In this study, we investigated the LRP8/signal transducer and activator of transcription 3 (STAT3)/PD-L1 network in osteosarcoma. Methods: The expression of LRP8, STAT3, and PD-L1 was measured in osteosarcoma tissues and paired normal tissues. The effects of LRP8 on STAT3 and PD-L1 expression were investigated in an osteosarcoma cell line. The effects on immunosuppression were investigated in an in vitro co-culture system with Jurkat cell line and osteosarcoma cell line. The effects of LRP8 were blocked by a LRP8 neutralizing antibody, dominant-negative STAT3, or STAT3 inhibitor. Results: LRP8 was overexpressed in osteosarcoma compared to normal tissues and its level was correlated with phospho-STAT3 (p-STAT3) level in osteosarcoma tissues. In osteosarcoma cell lines, LRP8 increased p-STAT3 level and promoted nuclear translocation of STAT3. STAT3 activation also increased PD-L1 mRNA, protein, and promoter activity. In addition, LRP8 enhanced PD-L1 expression via STAT3. In a co-culture system, LRP8 overexpression in an osteosarcoma cell line impaired viability and interleukin-2 secretion of Jurkat cells and induced apoptosis of Jurkat cells. The effects of LRP8 could be blocked by neutralizing LRP8 antibody or STAT3 inhibitor. Blocking LRP8 inhibits proliferation and induces apoptosis of osteosarcoma cells. Conclusions: Our results provide evidence for a novel regulation network of LRP8/STAT3/PD-L1 in osteosarcoma and LRP8 may be a potential therapeutic target in osteosarcoma.

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The Role of Alpha-Lipoic Acid in the Pathomechanism of Acute Ischemic Stroke

Cellular Physiology and Biochemistry ◽

10.1159/000491661 ◽

2018 ◽

Vol 48 (1) ◽

pp. 42-53 ◽

Cited By ~ 6

Author(s):

Qingqing Wang ◽

Chengmei Lv ◽

Yongxin Sun ◽

Xu Han ◽

Shan Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

Lipoic Acid ◽

Nuclear Translocation ◽

Infarct Volume ◽

Neurological Deficits ◽

Experimental Stroke ◽

Enzyme Linked Immunosorbent Assay ◽

M2 Phenotype

Background/Aims: Ischemic stroke results in increased cerebral infarction, neurological deficits and neuroinflammation. The underlying mechanisms involving the anti-inflammatory and neuroprotective properties of α-Lipoic acid (α-LA) remain poorly understood. Herein, we investigated the potential role of α-LA in a middle cerebral artery occlusion (MCAO) rat model and an in vitro lipopolysaccharide (LPS)-induced microglia inflammation model. Methods: In the in vivo study, infarct volume was examined by TTC staining and Garcia score was used to evaluate neurologic recovery. The cytokines were evaluated by enzyme-linked immunosorbent assay, and protein expression of microglia phenotype and NF-κB were measured using western blot. In the in vitro study, the expressions of microglia M1/M2 phenotype were evaluated using qRT-PCR, and immunofluorescence staining was used to assess the nuclear translocation of NF-κB. Results: Both 20 mg/kg and 40 mg/kg of α-LA alleviated infarct size, brain edema, and neurological deficits. Furthermore, α-LA induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-1β, IL-6, TNF-α and IL-10, and attenuated the activation of NF-κB after MCAO. α-LA inhibited the expression of M1 markers, increased activation of the M2 markers, and suppressed the nuclear translocation of NF-κB in LPS-stimulated BV2 microglia. Conclusions: α-LA improved neurological outcome in experimental stroke via modulating microglia M1/M2 polarization. The potential mechanism of α-LA might be mediated by inhibition of NF-κB activation via regulating phosphorylation and nuclear translocation of p65.

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The composite sandwich structure of dNCPs polyelectrolyte multilayers induced the osteogenic differentiation of PDLSCs in vitro

Journal of Applied Biomaterials & Functional Materials ◽

10.1177/2280800020942719 ◽

2020 ◽

Vol 18 ◽

pp. 228080002094271

Author(s):

Jing Chen ◽

Wenxing Li ◽

Qiang Li ◽

Yuhui Wang ◽

Bingjiao Zhao ◽

...

Keyword(s):

Osteogenic Differentiation ◽

Sandwich Structure ◽

Polyelectrolyte Multilayers ◽

Osteogenic Potential ◽

Fiber Morphology ◽

Periodontal Ligament Stem Cells ◽

Composite Sandwich ◽

Coated Membranes ◽

Experimental Group

This study reported about the fabrication of dentin non-collagenous proteins (dNCPs) polyelectrolyte multilayers and evaluated its osteogenic potential. The composite sandwich structure of dNCPs polyelectrolyte multilayers was generated on the surface of polycaprolactone electrospinning membranes by the Layer-by-Layer self-assembly technique. The dNCPs-coated membranes comprised the experimental group and the non-coated membranes acted as the control. Nanofiber morphologies of both membranes were observed under scanning electron microscope. The release of dNCPs was evaluated by ELISA kit. Periodontal ligament stem cells (PDLSCs) were seeded on both membranes. The morphology changes and proliferation of cells were tested. The expressions of osteogenic-related genes and proteins were evaluated by RT-PCR, alkaline phosphatase (ALP) activity assay, and immunofluorescence staining. dNCPs-coated membranes displayed significantly different fiber morphology than the non-coated membranes. A stable release of dentin phosphoprotein was maintained from day 4 to day 15 in the experimental group. Cells on dNCPs-coated membranes were found to have cuboidal or polygonal shapes. The proliferative rate of cells was significantly lower in the experimental group from day 4 to day 9 ( p<0.05). However, cells on the dNCPs-coated membranes demonstrated a significantly higher ALP content and expression levels of osteogenic gene and proteins than the controls ( p<0.05). These results indicated that dNCPs polyelectrolyte multilayers could induce the osteogenic differentiation of PDLSCs in vitro.

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MPC1 Deficiency Promotes CRC Liver Metastasis via Facilitating Nuclear Translocation of β-Catenin

Journal of Immunology Research ◽

10.1155/2020/8340329 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Guang-Ang Tian ◽

Chun-Jie Xu ◽

Kai-Xia Zhou ◽

Zhi-Gang Zhang ◽

Jian-Ren Gu ◽

...

Keyword(s):

Tumor Metastasis ◽

Nuclear Translocation ◽

Tca Cycle ◽

Mitochondrial Pyruvate Carrier ◽

Human Sample ◽

Metastatic Capacity ◽

Tcga Dataset

Accumulating evidence has pointed out that metastasis is the leading cause of death in several malignant tumor, including CRC. During CRC, metastatic capacity is closely correlated with reprogrammed energy metabolism. Mitochondrial Pyruvate Carrier 1 (MPC1), as the carrier of transporting pyruvate into mitochondria, linked the glycolysis and TCA cycle, which would affect the energy production. However, the specific role of MPC1 on tumor metastasis in CRC remains unexplored. Here, by data mining of genes involved in pyruvate metabolism using the TCGA dataset, we found that MPC1 was significantly downregulated in CRC compared to nontumor tissues. Similar MPC1 expression pattern was also found in multiple GEO datasets. IHC staining in both human sample and AOM/DSS induced mouse CRC model revealed significant downregulation of MPC1. What is more, we found that MPC1 expression was gradually decreased in normal tissue, primary CRC, and metastasis CRC. Additionally, poor prognosis emerged in the MPC1 low expression patients, especially in patients with metastasis. Following, functional tests showed that MPC1 overexpression inhibited the motility of CRC cells in vitro and MPC1 silencing enhanced liver metastases in vivo. Furthermore, we uncovered that decreased MPC1 activated the Wnt/β-catenin pathway by promoting nuclear translocation of β-catenin to mediate the expression of MMP7, E-cadherin, Snail1, and myc. Collectively, our data suggest that MPC1 has the potential to be served as a promising biomarker for diagnosis and a therapeutic target in CRC.

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