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https://www.readbyqxmd.com/read/27897113/strong-association-of-lipid-metabolism-related-microrna-binding-sites-polymorphisms-with-the-risk-of-late-onset-alzheimer-s-disease
#1
Lin Tan, Da-Long Zhao, Fu-Rong Sun, Meng-Shan Tan, Yu Wan, Chen-Chen Tan, Wei Zhang, Dan Miao, Jin-Tai Yu, Lan Tan
Although altered lipid metabolism has been extensively implicated in the pathogenesis of late onset Alzheimer's disease (LOAD) through cell biological and epidemiological studies, genetic studies linking lipid metabolism and LOAD are still not well understood. MicroRNAs (miRNAs) exert post-transcriptional down-regulation and their target sequence on the 3' untranslated regions (3'UTR) may be altered by single nucleotide polymorphisms (SNPs). We therefore explore whether the six loci in Clusterin gene (CLU) (rs9331949), Lipoprotein lipase gene (LPL) (rs1059507, rs3200218, rs3208305, rs3735964) and Low-density lipoprotein receptor related protein 6 (LRP6) (rs2160525) could modulate LOAD risk through the alteration of miRNA binding sites...
October 27, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27893427/cholesterol-import-and-steroidogenesis-are-biosignatures-for-gastric-cancer-patient-survival
#2
Wei-Chun Chang, Shang-Fen Huang, Yang-Ming Lee, Hsueh-Chou Lai, Bi-Hua Cheng, Wei-Chung Cheng, Jason Yen-Ping Ho, Long-Bin Jeng, Wen-Lung Ma
Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27868125/coumestrol-modulates-akt-and-wnt-%C3%AE-catenin-signaling-during-the-attenuation-of-adipogenesis
#3
Young Jin Jang, Hyo Jeong Son, Jiyun Ahn, Chang Hwa Jung, Taeyoul Ha
Coumestrol is a natural phytochemical present in plants such as red clover and soy, and has been reported to stimulate the estrogen receptor as a major phytoestrogen. While the molecular mechanisms responsible for the anti-adipogenic effects of phytoestrogens such as genistein and daidzein have been previously investigated, the effects of coumestrol on adipogenesis remain to be elucidated. We observed that coumestrol dose-dependently attenuates MDI (mixture of 3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-induced lipid accumulation, consistent with an earlier study, while significantly inhibiting MDI-induced adipogenesis in the first 48 hours of differentiation, a critical time window for anti-adipogenic effects...
November 21, 2016: Food & Function
https://www.readbyqxmd.com/read/27864382/molecular-dynamics-of-dkk4-modulates-wnt-action-and-regulates-meibomian-gland-development
#4
Jian Sima, Yulan Piao, Yaohui Chen, David Schlessinger
Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, similar to that observed in Eda-ablated Tabby mice...
November 18, 2016: Development
https://www.readbyqxmd.com/read/27854329/mir-30e-5p-and-mir-15a-synergistically-regulate-fatty-acid-metabolism-in-goat-mammary-epithelial-cells-via-lrp6-and-yap1
#5
Zhi Chen, Huiling Qiu, Liuan Ma, Jun Luo, Shuang Sun, Kang Kang, Deming Gou, Juan J Loor
MicroRNA (miRNA) regulates the expression of genes and influences a series of biological processes, including fatty acid metabolism. We screened the expression of miRNA in goat mammary glands during peak-lactation and non-lactating ("dry") periods, and performed an in vitro study with goat mammary epithelial cells (GMEC) prior to sequencing analysis. Results illustrated that miR-30e-5p and miR-15a were highly expressed. Utilizing a luciferase reporter assay and Western blot, low-density lipoprotein receptor-related protein 6 (LRP6) and Yes associated protein 1 (YAP1) genes were demonstrated to be a target of miR-30e-5p and miR-15a in GMEC...
November 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27821587/caprin-2-positively-regulates-cdk14-cyclin-y-mediated-lrp5-6-constitutive-phosphorylation
#6
Xin Wang, Yingying Jia, Cong Fei, Xiaomin Song, Lin Li
Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are co-receptors for Wnt ligands. Upon ligand binding, LRP5/6 undergoes GSK3/CKI-mediated phosphorylation at multiple PPP(S/T)P motifs in the intracellular domain (ICD), which is essential for the canonical Wnt signal transduction. On the other hand, in Wnt-off state, the mitosis-specific CDK14/Cyclin Y kinase complex phosphorylates the S1490 of LRP5/6 at G2/M, thereby priming the receptor for Wnt-induced phosphorylation. However, it remains unclear how CDK14/Cyclin Y is recruited to LRP5/6 and whether there are other cofactors involved in this process...
November 7, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27806330/plasma-glutamate-carboxypeptidase-is-a-negative-regulator-in-liver-cancer-metastasis
#7
Jae-Hye Lee, Hyun-Soo Cho, Jeong-Ju Lee, Soo Young Jun, Jun-Ho Ahn, Ju-Sik Min, Ji-Yong Yoon, Min-Hyuk Choi, Su-Jin Jeon, Jung Hwa Lim, Cho-Rok Jung, Dae-Soo Kim, Hyun-Taek Kim, Valentina M Factor, Yun-Han Lee, Snorri S Thorgeirsson, Cheol-Hee Kim, Nam-Soon Kim
Tumor metastasis is the leading cause of cancer death. In the metastatic process, EMT is a unique phenotypic change that plays an important role in cell invasion and changes in cell morphology. Despite the clinical significance, the mechanism underlying tumor metastasis is still poorly understood. Here we report a novel mechanism by which secreted plasma glutamate carboxypeptidase(PGCP) negatively involves Wnt/β-catenin signaling by DKK4 regulation in liver cancer metastasis. Pathway analysis of the RNA sequencing data showed that PGCP knockdown in liver cancer cell lines enriched the functions of cell migration, motility and mesenchymal cell differentiation...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27799526/prodigiosin-inhibits-wnt-%C3%AE-catenin-signaling-and-exerts-anticancer-activity-in-breast-cancer-cells
#8
Zhongyuan Wang, Bo Li, Liang Zhou, Shubin Yu, Zijie Su, Jiaxing Song, Qi Sun, Ou Sha, Xiaomei Wang, Wenqi Jiang, Karl Willert, Lei Wei, Dennis A Carson, Desheng Lu
Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited promising anticancer activity; however, the molecular mechanisms of action of prodigiosin on malignant cells remain unclear. Aberrant activation of the Wnt/β-catenin signaling cascade is associated with numerous human cancers. In this study, we identified prodigiosin as a potent inhibitor of the Wnt/β-catenin pathway. Prodigiosin blocked Wnt/β-catenin signaling by targeting multiple sites of this pathway, including the low-density lipoprotein-receptor-related protein (LRP) 6, Dishevelled (DVL), and glycogen synthase kinase-3β (GSK3β)...
October 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27789627/filamin-a-and-formin-2-dependent-endocytosis-regulates-proliferation-via-the-canonical-wnt-pathway
#9
Gewei Lian, Markus Dettenhofer, Jie Lu, Michael Downing, Anjen Chenn, Timothy Wong, Volney Sheen
Actin-associated proteins regulate multiple cellular processes, including proliferation and differentiation, but the molecular mechanisms underlying these processes are unclear. Here, we report that the actin-binding protein filamin A (FlnA) physically interacts with the actin-nucleating protein formin 2 (Fmn2). Loss of FlnA and Fmn2 impairs proliferation, thereby generating multiple embryonic phenotypes, including microcephaly. FlnA interacts with the Wnt co-receptor Lrp6. Loss of FlnA and Fmn2 impairs Lrp6 endocytosis, downstream Gsk3β activity, and β-catenin accumulation in the nucleus...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27780792/application-of-anti-sclerostin-therapy-in-non-osteoporosis-disease-models
#10
Christina M Jacobsen
Sclerostin, a known inhibitor of the low density lipoprotein related protein 5 and 6 (LRP5 and LRP6) cell surface signaling receptors, is integral in the maintenance of normal bone mass and strength. Patients with loss of function mutations in SOST or missense mutations in LRP5 that prevent Sclerostin from binding and inhibiting the receptor, have significantly increased bone mass. This observation leads to the development of Sclerostin neutralizing therapies to increase bone mass and strength. Anti-Sclerostin therapy has been shown to be effective at increasing bone density and strength in animal models and patients with osteoporosis...
October 22, 2016: Bone
https://www.readbyqxmd.com/read/27754059/os-15-07-role-of-pro-renin-receptor-in-the-activation-of-wnt-%C3%AE-catenin-pathway-in-colon-cancer
#11
Juan Wang, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
OBJECTIVE: Constitutive activation of Wnt/β-catenin pathway plays an important role in the pathogenesis of colon cancer; however, recent studies have also indicated that elevated Wnt levels are essential. In the present study, we investigated the potential role of (pro) renin receptor in the pathophysiology of colon cancer. DESIGN AND METHOD: (P) RR expression in human colon tissues was measured by immunohistochemistry and Western blot analysis. Human colon cancer cell lines DLD-1 with adenomatous polyposis coli (APC) truncated mutation, and HCT116 withβ-catenin activating mutation, were transfected with scramble siRNA and siRNA against (pro) renin receptor...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27751231/ubiquitin-dependent-folding-of-the-wnt-signaling-coreceptor-lrp6
#12
Elsa Perrody, Laurence Abrami, Michal Feldman, Beatrice Kunz, Sylvie Urbé, F Gisou van der Goot
Many membrane proteins fold inefficiently and require the help of enzymes and chaperones. Here we reveal a novel folding assistance system that operates on membrane proteins from the cytosolic side of the endoplasmic reticulum (ER). We show that folding of the Wnt signaling coreceptor LRP6 is promoted by ubiquitination of a specific lysine, retaining it in the ER while avoiding degradation. Subsequent ER exit requires removal of ubiquitin from this lysine by the deubiquitinating enzyme USP19. This ubiquitination-deubiquitination is conceptually reminiscent of the glucosylation-deglucosylation occurring in the ER lumen during the calnexin/calreticulin folding cycle...
October 18, 2016: ELife
https://www.readbyqxmd.com/read/27723935/n-cadherin-restrains-pth-repressive-effects-on-sclerostin-sost-by-regulating-lrp6-pth1r-interaction
#13
Hailin Yang, Jinbo Dong, Wei Xiong, Zhong Fang, Hanfeng Guan, Feng Li
Sclerostin/SOST is a robust negative regulator of bone formation. Loss-of-function mutations of the sclerostin gene (SOST) cause sclerosteosis and Van Buchem disease characterized by bone overgrowth. Mediated by myocyte enhancer factor 2 (MEF2) transcription factors, parathyroid hormone (PTH) suppresses SOST expression through formation of complexes of parathyroid hormone-parathyroid hormone-related peptide receptor 1 (PTH1R) and lipoprotein receptor-related protein 6 (LRP6). N-cadherin has been shown to negatively regulate Wnt/β-catenin and PTH induced, protein kinase-dependent β-catenin signaling...
October 10, 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/27720905/a-dynamic-wnt-%C3%AE-catenin-signaling-environment-leads-to-wnt-independent-and-wnt-dependent-proliferation-of-embryonic-intestinal-progenitor-cells
#14
Alana M Chin, Yu-Hwai Tsai, Stacy R Finkbeiner, Melinda S Nagy, Emily M Walker, Nicole J Ethen, Bart O Williams, Michele A Battle, Jason R Spence
Much of our understanding about how intestinal stem and progenitor cells are regulated comes from studying the late fetal stages of development and the adult intestine. In this light, little is known about intestine development prior to the formation of stereotypical villus structures with columnar epithelium, a stage when the epithelium is pseudostratified and appears to be a relatively uniform population of progenitor cells with high proliferative capacity. Here, we investigated a role for WNT/β-CATENIN signaling during the pseudostratified stages of development (E13...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27713038/validation-of-recently-proposed-colorectal-cancer-susceptibility-gene-variants-in-an-analysis-of-families-and-patients-a-systematic-review
#15
Peter Broderick, Sara E Dobbins, Daniel Chubb, Ben Kinnersley, Malcolm G Dunlop, Ian Tomlinson, Richard S Houlston
High-throughput sequencing analysis has accelerated searches for genes associated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1, TP53, BUB1, BUB3, LRP6, and PTPN12 have been recently proposed to increase CRC risk. We attempted to validate the association between variants in these genes and development of CRC in a systematic review of 11 publications, using sequence data from 863 familial CRC cases and 1604 individuals without CRC (controls). All cases were diagnosed at an age of 55 years or younger and did not carry mutations in an established CRC predisposition gene...
October 3, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27709494/identification-of-noncanonical-wnt-receptors-required-for-wnt-3a-induced-early-differentiation-of-human-neural-stem-cells
#16
Nora Bengoa-Vergniory, Irantzu Gorroño-Etxebarria, Inmaculada López-Sánchez, Michele Marra, Pierluigi Di Chiaro, Robert Kypta
Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a...
October 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27680891/macrophages-of-genetically-characterized-familial-hypercholesterolaemia-patients-show-up-regulation-of-ldl-receptor-related-proteins
#17
Rafael Escate, Teresa Padro, Maria Borrell-Pages, Rosa Suades, Rosa Aledo, Pedro Mata, Lina Badimon
Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL...
September 29, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27642979/os-15-07-role-of-pro-renin-receptor-in-the-activation-of-wnt-%C3%AE-catenin-pathway-in-colon-cancer
#18
Juan Wang, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
OBJECTIVE: Constitutive activation of Wnt/β-catenin pathway plays an important role in the pathogenesis of colon cancer; however, recent studies have also indicated that elevated Wnt levels are essential. In the present study, we investigated the potential role of (pro) renin receptor in the pathophysiology of colon cancer. DESIGN AND METHOD: (P) RR expression in human colon tissues was measured by immunohistochemistry and Western blot analysis. Human colon cancer cell lines DLD-1 with adenomatous polyposis coli (APC) truncated mutation, and HCT116 withβ-catenin activating mutation, were transfected with scramble siRNA and siRNA against (pro) renin receptor...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27635281/mice-with-a-heterozygous-lrp6-deletion-have-impaired-fracture-healing
#19
Travis A Burgers, Juan F Vivanco, Juraj Zahatnansky, Andrew J Vander Moren, James J Mason, Bart O Williams
Bone fracture non-unions, the failure of a fracture to heal, occur in 10%-20% of fractures and are a costly and debilitating clinical problem. The Wnt/β-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 (LRP6), a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density...
2016: Bone Research
https://www.readbyqxmd.com/read/27592552/wnt-%C3%AE-catenin-signaling-plays-a-distinct-role-in-methyl-gallate-mediated-inhibition-of-adipogenesis
#20
Miso Jeon, Naimur Rahman, Yong-Sik Kim
The canonical Wnt/β-catenin signaling not only features in many developmental processes but also recently emerged as an attractive negative regulator of differentiation of preadipocytes into adipocytes. Here, we show that β-catenin signaling plays a distinct role in methyl gallate (MG)-mediated inhibition of 3T3-L1 adipocytes differentiation. We found that the expression of β-catenin decreased after adipogenic hormonal induction, whereas incubation of the differentiating cells with a physiological concentration of MG during adipogenic hormonal induction significantly prevented β-catenin degradation by activating Wnt signaling components such as Wnt1, Wnt10b, Fzd1, Fzd2, Lrp5, Lrp6, Dvl1, and Dvl2...
October 7, 2016: Biochemical and Biophysical Research Communications
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