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Yin W.,State Key Laboratory of Medical Genetics | Liu H.,State Key Laboratory of Medical Genetics | Peng Z.,State Key Laboratory of Medical Genetics | Chen D.,State Key Laboratory of Medical Genetics | And 3 more authors.
Cellular Signalling | Year: 2014

Prokineticins (PKs) are a pair of signal factors involved in many physiological processes by binding to two closely related G-protein-coupled receptors (GPCRs), PKR1 and PKR2. We recently demonstrated that PKR2 undergoes rapid ligand-induced endocytosis, and PKR2 recycles back to the plasma membrane after the removal of ligand. However, little is known about the molecular mechanisms underlying the PKR2 endocytosis. Here, we studied the involvement of GPCR kinase 2 (GRK2), β-arrestins, clathrin and protein kinase C (PKC) in the PKR2 endocytosis. Our results indicated that PK2-induced PKR2 endocytosis is GRK2- and clathrin-dependent, but β-arrestin-independent. PKC activation also induced PKR2 endocytosis; however, PKC activation is not necessary for the PK2-induced PKR2 endocytosis. PK2 stimulation induced a transient activation of extracellular signal regulated kinase 1/2 (ERK1/2) on PKR2 expressing cells. The internalization and PKC activation are not required for the PK2-induced ERK1/2 activation. Our results indicated that PK2-induced ERK1/2 activation may involve the released βγ subunits of G-protein, phospholipase C β and MEK activation. © 2014 Elsevier Inc. Source

Zhou J.,Central South University | Liu R.,Central South University | Luo C.,Central South University | Zhou X.,Affiliated Tumor Hospital of Xiangya Medical School | And 6 more authors.
Cancer Biology and Therapy | Year: 2014

Background: MicroRNA-20a (miR-20a) plays a key role in tumorigenesis and progression. But its function is reverse in different kinds of malignant tumor, and its role and mechanism in cutaneous squamous cell carcinoma (CSCC) remains unclear.Object: To determine the miR-20a's roles in CSCC and confirm whether LIMK1 is a direct target gene of miR-20a.Methods: First miR-20a and LIMK1 expression levels were detected in six pairs of CSCC tissues and corresponding normal skin by qRT-PCR. Then MTT assays and colony formation assays were performed to evaluate the impact of miR-20a on cell proliferation. In addition, scratch migration assays and transwell invasion assays were performed to check miR-20a's effect on cell metastasis. Since LIMK1 (LIM kinase-1) was predicted as a target gene of miR-20a, the changes of LIMK1 protein and mRNA were measured by western blot and qRT-RCR methods after miR-20a overexpression. Moreover the dual reporter gene assay was performed to confirm whether LIMK1 is a direct target gene of miR-20a. Finally LIMK1 mRNA and miR-20a in other 30 cases of CSCC pathological specimens were determined and a correlation analysis was evaluated.Results: The miR-20a significantly low-expressed in CSCC tissues compared with that in matched normal tissues while LIMK1 has a relative higher expression. MiR-20a inhibited a431 and sCL-1 proliferation and metastasis. Both of LIMK1 protein and mRNA levels were downregulated after miR-20a overexpression. The dual reporter gene assays revealed that LIMK1 is a direct target gene of miR-20a. Furthermore, qRT-PCR results of LIMK1 mRNA and miR-20a in 30 cases of CSCC pathological specimens showed miR-20a is inversely correlated with LIMK1 expression.Conclusion: Our study demonstrated that miR-20a is involved in the tumor inhibition of CSCC by directly targeting LIMK1 gene. This finding provides potential novel strategies for therapeutic interventions of CSCC. © 2014 Landes Bioscience. Source

Li M.,Central South University | Li M.,State Key Laboratory of Medical Genetics | Wu X.,Central South University | Pan Y.,Central South University | And 2 more authors.
Proteomics | Year: 2013

Clustering of protein-protein interaction networks is one of the most prevalent methods for identifying protein complexes, detecting functional modules and predicting protein functions. In the past few years, many clustering methods have been proposed. However, it is still a challenging task to evaluate how well the protein clusters are identified. Even for two of the most popular measurements, F-measure and p-value, bias exists when evaluating the identified clusters. In this paper, we propose two new types of measurements to evaluate clusters more finely and distinctly. One is hF-measureTf, a topology-free measurement and another is hF-measureTb, a topology-based measurement. Unlike F-measure, the new measurements of hF-measureTf and hF-measureTb can discriminate between different types of errors. Both artificial test data and practical test data were used to evaluate the effectiveness of hF-measureTf and hF-measureTb. For the artificial test data, artificial errors were generated by replacing some cluster members with functionally similar or non-similar members. The practical test data was produced by seven clustering algorithms Markov Clustering, Molecular Complex Detection, HC-PIN, SPICI, CPM, Core-Attachment and RRW. The experimental results on artificial and practical test data both show that hF-measureTf and hF-measureTb evaluate clusters more accurately compared to F-measure. Especially, hF-measureTb can capture the topology changes in clusters, which can also be used to the analysis of dynamic network. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Long D.,Central South University | Zeng J.,Central South University | Wu L.Q.,State Key Laboratory of Medical Genetics | Tang L.S.,Central South University | And 2 more authors.
Ophthalmic Genetics | Year: 2012

Objective: To describe the clinical and pathological findings of two large mainland Chinese kindreds with vitreous amyloidosis and associated transthyretin mutation. Methods: Twenty individuals from two kindreds with vitreous amyloidosis were ascertained. The transtheretin (TTR) gene of each individual was analyzed, and a clinical examination was obtained on the index patient. Results: Vitreous amyloidosis and radiculopathy were the significant findings in affected individuals. Vitrectomy was performed on the severely affected individuals, with resulting postoperative visual acuity of 20/80 to 20/25. Congo red staining demonstrated amyloid in the vitreous specimen. In Case A, DNA sequencing of exon 2 in the TTR gene revealed a base-pair substitution at codon 35, AAG>ACG (Lys35Thr). In Case B, a missense mutation of leucine-to-arginine substitution was identified at amino acid position 55 in exon 3, CTG>CGG (Leu55Arg). Conclusions: TTR Lys35Thr and Leu55Arg mutations are associated with vitreous amyloidosis. The phenotype is variable, with vitreous opacities occurring earlier, and sometimes as the sole signs of amyloidotic polyneuropathies (FAPs). Vitrectomy improves vision in some patients with vitreous amyloidosis. © 2012 Informa Healthcare USA, Inc. Source

Guo H.,State Key Laboratory of Medical Genetics | Tong P.,The Second Xiangya Hospital | Peng Y.,State Key Laboratory of Medical Genetics | Wang T.,State Key Laboratory of Medical Genetics | And 13 more authors.
Clinical Genetics | Year: 2014

High myopia is a severe visual impairment which can increase the risk of retinal degeneration, subretinal hemorrhage, choroidal neovascularization, cataract and retinal detachment. We recruited an autosomal-recessive high myopia family, with affected subjects who also present early-onset cataract, retinal degeneration and other complications. Using targeted capturing and whole exome sequencing, we identified a homozygous non-sense mutation in the LEPREL1 gene which causes premature termination of the translation at the fifth amino acid (c.13C>T; p.Q5X), co-segregating with the phenotypes. LEPREL1 encodes a proline hydroxylase called prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The results show that LEPREL1 plays an important role in eye development and homozygous loss-of-function mutation of this gene can cause severely high myopia and early-onset cataract. Our study also strongly suggests that the disruption of collagen modification is one of the pathogenic mechanisms of high myopia and cataract. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

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