Huancai Liu

Weifang Medical University, Wei, Shandong Sheng, China

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Publications (4)9.03 Total impact

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    ABSTRACT: Autophagy is an intracellular degradation process that clears away aggregated proteins or aged and damaged organelles. Abnormalities in autophagy result in defects in clearance of these misfolded and aggregate proteins, which have been associated with neurodegenerative disorders. A key neuropathological hallmark of amyotrophic lateral sclerosis (ALS) that contributes to the progressive loss of motor neurons is abnormal protein aggregation of mutant Cu/Zn superoxide dismutase1 (SOD1). TFEB is a recently described gene that regulates autophagy. Several studies have reported that autophagy is altered in ALS, but little is known about the role and mechanisms of TFEB-mediated autophagy during the progression of ALS. In this study, altered expression of TFEB and Beclin-1 were detected in the spinal cords of ALS transgenic mice at different stages and in an NSC-34 cell model with the SOD1-G93A mutation using RT-PCR, western blot, and immunohistochemistry. The majority of cells positive for TFEB and Beclin-1 are β-tubulin III-labeled neurons, especially in the anterior horn of the gray matter. Overexpression of TFEB in NSC-34 cells with the SOD1-G93A mutation increased the mRNA and protein levels of Beclin-1, accompanied by increased levels of LC3-II protein. MTS assay revealed that TFEB overexpression increased proliferation and survival of NSC-34 cells with the SOD1-G93A mutation. Our findings suggest that TFEB promotes autophagy by enhancing the expression of Beclin-1. The altered autophagy mediated by TFEB is a key element in the pathogenesis of ALS, making TFEB a very promising target for the development of novel drugs and new gene therapeutics for ALS.
    No preview · Article · Nov 2015 · American Journal of Translational Research
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    ABSTRACT: Osteosarcoma (OS) is the most common primary malignant bone tumor that has poor prognosis. Molecular mechanisms underlying disease progression remain largely unknown. Sox9, one of the Sox family transcription factors, is closely associated with the development of a variety of malignant tumors. This study investigates the expression of Sox9, Wnt1 and Fzd1 in human osteosarcoma tissues and cells and the role of Sox9 in the proliferation of human osteosarcoma cells. Immunohistochemical analyses for Sox9, Wnt1, Fzd1, and Ki-67 proteins were performed in human primary osteosarcoma tissues from 48 patients. The small interfering RNA (siRNA) of Sox9 was transfected into human osteosarcoma MG63 cells. At 24 and 48 h after transfection with Sox9 siRNA, the expression of Wnt1 and Fzd1 was analyzed by RT-qPCR, Western blot, and immunofluorescence techniques. Cell proliferation was assayed by CCK-8 method, and Ki-67 protein expression was analyzed by Western blot. Results showed that the expressions of Sox9, Wnt1, Fzd1, and Ki-67 proteins in human osteosarcoma tissues were higher than those in the adjacent non-cancerous tissues. Hyperexpressions of Sox9, Wnt1, Fzd1, and Ki-67 proteins occurred more frequently in human osteosarcoma tissues with an advanced clinical stage (IIb/III). Sox9 siRNA reduced both mRNA and protein expression levels of Wnt1 and Fzd1, which result in the distinct inhibition of MG63 cell proliferation. Our study suggests that Sox9 siRNA inhibits the proliferation capability of human osteosarcoma cells by down-regulating the expression of Wnt1 and its receptor Fzd1, which may provide new gene targets for the clinical treatment of osteosarcoma.
    No preview · Article · Sep 2014 · International journal of clinical and experimental pathology
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    ABSTRACT: Our aim was to examine the change in expression of molecules involved in Wnt signaling in the pathogenesis of amyotrophic lateral sclerosis (ALS) in adult transgenic mice, and to reveal the relationship between the Wnt signaling pathway and the pathogenesis of ALS. We determined the expression of Wnt2, Wnt7a, and GSK-3beta in the spinal cord of SOD1(G93A) ALS transgenic mice at different ages using reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry. Using double labeling, we determined whether Wnt2, Wnt7a, and GSK-3beta were colocalized with beta-tubulin III, for neurons, or glial fibrillary acidic protein, for mature astrocytes. Wnt2, Wnt7a mRNA and protein in the spinal cord of ALS mice were upregulated and compared with wild-type mice. Phospho-GSK-3beta (Ser 9) protein levels in the spinal cord of ALS mice were upregulated. Moreover, the immunoreactivity of Wnt2, Wnt7a, and phospho-GSK-3beta (Ser 9) was strong in ALS mice but weak in wild-type mice at the same time points. Double immunofluorescence labeling showed that Wnt2 and Wnt7a were expressed in both neurons and astrocytes, whereas GSK-3beta was expressed only in neurons. Most of the double positive cells were located in the ventral horns of the gray matter, the locus of neurodegeneration. Neurodegeneration upregulated the expression of Wnt2 and Wnt7a in the spinal cord of ALS mice, which in turn activated Wnt signaling, and accordingly inhibited GSK-3beta activity in disease progression of ALS in adult transgenic mice; this could regulate the downstream gene of the Wnt signaling pathway and promote cell proliferation.
    No preview · Article · May 2012 · Neurological Research
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. Wnt3a, β-catenin, and Cyclin D1 are three key signaling molecules of the Wnt/β-catenin signaling pathway. We determined the expression of Wnt3a, β-catenin, and Cyclin D1 in the adult spinal cord of SOD1(G93A) ALS transgenic mice at different stages by RT-PCR, Western blot, and immunofluorescence labeling techniques. We found that the mRNA and protein of Wnt3a and Cyclin D1 in the spinal cord of the ALS mice were upregulated compared to those in wild-type mice. In addition, β-catenin translocated from the cell membrane to the nucleus and subsequently activated transcription of the target gene, Cyclin D1. BrdU and Cyclin D1 double-positive cells were increased in the spinal cord of these mice. Moreover, Wnt3a, β-catenin, and Cyclin D1 were also expressed in both neurons and astrocytes. The expression of Wnt3a, β-catenin or Cyclin D1 in mature GFAP(+) astrocytes increased. Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that neurodegeneration activates the Wnt/β-catenin signaling pathway, which is associated with glial proliferation in the adult spinal cord of ALS transgenic mice. This mechanism may be significant in clinical gene therapy.
    No preview · Article · Mar 2012 · Biochemical and Biophysical Research Communications