Human LOXL2 ELISA Kit

Product Datasheet Human LOXL2 ELISA Kit Catalog No: #EK5643 Orders: [email protected] Description Support: [email protected] Product Name Human LOXL2 ELISA Kit Specificity Human Crossing Reactivity There is no detectable cross-reactivity with other relevant proteins. Immunogen Type NSO, Q26-Q774 Other Names Lysyl oxidase homolog 2; 1.4.3.13; Lysyl oxidase-like protein 2; Lysyl oxidase-related protein 2; Lysyl oxidase-related protein WS9-14; LOXL2; Accession No. Q9Y4K0 Cell Localization Secreted, extracellular space, extracellularmatrix, basement membrane. Nucleus. Chromosome.Associated with chromatin. It is unclear how LOXL2 isnuclear: it contains a clear signal sequence and is predicted tolocalize in the extracellular medium. However, different reportsconfirmed the intracellular location and its key role intranscription regulation. Application Details sensitivity:10pg mlDetect Range:156pg ml-10 000pg mlsample_type:cell culture supernates cell lysates tissue homogenates serum and plasma(heparin EDTA).capture_antibody:monoclonal antibody from mousedetection_antibody:polyclonal antibody from goatgene_name:LOXL2protein_name:Lysyl oxidase homolog 2gene_full_name:Lysyl oxidase homolog 2tissue_specificity: Expressed in many tissues. Highest expressionin reproductive tissues placenta uterus and prostate. Up-regulated in a number of cancers cells and tissues.sequence_similarities:tmb_incubation:25-30minresearch_category:signal transduction|cytoskeleton / ecm|extracellular matrix|ecm enzymes enzymes|cancer|tumor biomarkers Product Description Sandwich High Sensitivity ELISA kit for Quantitative Detection of Human LOXL2 Background protein_function: Mediates the post-translational oxidative deamination oflysine residues on target proteins leading to the formation ofdeaminated lysine (allysine). When secreted in extracellularmatrix, promotes cross-linking of extracellular matrix proteins bymediating oxidative deamination of peptidyl lysine residues inprecursors to fibrous collagen and elastin. Acts as a regulator ofsprouting angiogenesis, probably via collagen IV scaffolding. Whennuclear, acts as a transcription corepressor and specificallymediates deamination of trimethylated "Lys-4" of histone H3(H3K4me3), a specific tag for epigenetic transcriptionalactivation. Involved in epithelial to mesenchymal transition (EMT)via interaction with SNAI1 and participates in repression of E-cadherin, probably by mediating deamination of histone H3. Alsoinvolved in E-cadherin repression following hypoxia, a hallmark ofepithelial to mesenchymal transition believed to amplify tumoraggressiveness, suggesting that it may play a role in tumorprogression. Acts as a regulator of chondrocyte differentiation,probably by regulating expression of factors that controlchondrocyte differentiation..Lysyl oxidase homolog 2 is an enzyme that in humans is encoded by the LOXL2 gene. This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. LOXL2 can also crosslink collagen type IV and hence influence the sprouting of new blood vessels. Address: 8400 Baltimore Ave., Suite 302, College Park, MD 20740, USA http://www.sabbiotech.com 1 Note: This product is for in vitro research use only and is not intended for use in humans or animals. Address: 8400 Baltimore Ave., Suite 302, College Park, MD 20740, USA http://www.sabbiotech.com 2.

Copy Link

Recommended publications

Human LOXL2 / Lysyl Oxidase Homolog 2 Protein (His Tag)
Human LOXL2 / Lysyl oxidase homolog 2 Protein (His Tag) Catalog Number: 11664-H08H General Information SDS-PAGE: Gene Name Synonym: LOR2; Lysyl oxidase-like 2; WS9-14 Protein Construction: A DNA sequence encoding the human LOXL2 (Q9Y4K0) (Met 1-Gln 774) was expressed, fused with a polyhistidine tag at the C-terminus. Source: Human Expression Host: HEK293 Cells QC Testing Purity: > 90 % as determined by SDS-PAGE Bio Activity： Protein Description Measured by its ability to produce hydrogen peroxide during the oxidation of benzylamine. The specific activity is > 2 pmoles/min/μg. Lysyl oxidase homolog 2, also known as Lysyl oxidase-like protein 2, Lysyl oxidase-related protein 2, Lysyl oxidase-related protein WS9-14 and Endotoxin: LOXL2, is a secreted protein which belongs to thelysyl oxidase family. LOXL2 contains fourSRCR domains. The lysyl oxidase family is made up < 1.0 EU per μg of the protein as determined by the LAL method of five members: lysyl oxidase (LOX) and lysyl oxidase-like 1-4 ( LOXL1, LOXL2, LOXL3, LOXL4 ). All members share conserved C-terminal Stability: catalytic domains that provide for lysyl oxidase or lysyl oxidase-like enzyme Samples are stable for up to twelve months from date of receipt at -70 ℃ activity; and more divergent propeptide regions. LOX family enzyme activities catalyze the final enzymatic conversion required for the formation Predicted N terminal: Gln 26 of normal biosynthetic collagen and elastin cross-links. LOXL2 is expressed by pre-hypertrophic and hypertrophic chondrocytes in vivo, and Molecular Mass: that LOXL2 expression is regulated in vitro as a function of chondrocyte differentiation.
[Show full text]
The Function and Mechanisms of Action of LOXL2 in Cancer (Review)
1200 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 36: 1200-1204, 2015 The function and mechanisms of action of LOXL2 in cancer (Review) LINGHONG WU and YING ZHU Department of Infectious Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China Received May 31, 2015; Accepted August 26, 2015 DOI: 10.3892/ijmm.2015.2337 Abstract. The lysyl oxidase (LOX) family is comprised of five copper‑dependent amine oxidase, and its main role is to members, and some members have recently emerged as impor- catalyze the covalent cross‑link of collagen and elastin in tant regulators of tumor progression. Among these, at present, the extracellular matrix (ECM). This occurs through the LOX‑like (LOXL)2 is the prototypical LOX and the most oxidative deamination of peptidyl lysine residues in ECM comprehensively studied member. A growing body of evidence components (1,2). Each member of the LOX family has a has implicated LOXL2 in the promotion of cancer cell inva- highly conserved carboxyl (C)‑terminal domain that contains a sion, metastasis and angiogenesis, as well as in the malignant copper‑binding motif, lysine tyrosylquinone (LTQ) residues and transformation of solid tumors. Moreover, a high expression of a cytokine receptor‑like (CRL) domain, which is essential for LOXL2 is associated with a poor prognosis. These data have catalytic activity (3). The amino‑terminal regions are different piqued the interest of a number of researchers and research and are thought to be important in protein‑protein interactions. groups, who have identified LOXL2 as a strong target candidate The prodomains in LOX and LOXL1 enable their secretion in the development of inhibitors for use as functional and effi- as inactive proenzymes, which are then activated extracel- cacious tumor therapeutics.
[Show full text]
LOXL1 Confers Antiapoptosis and Promotes Gliomagenesis Through Stabilizing BAG2
Cell Death & Differentiation (2020) 27:3021–3036 https://doi.org/10.1038/s41418-020-0558-4 ARTICLE LOXL1 confers antiapoptosis and promotes gliomagenesis through stabilizing BAG2 1,2 3 4 3 4 3 1 1 Hua Yu ● Jun Ding ● Hongwen Zhu ● Yao Jing ● Hu Zhou ● Hengli Tian ● Ke Tang ● Gang Wang ● Xiongjun Wang1,2 Received: 10 January 2020 / Revised: 30 April 2020 / Accepted: 5 May 2020 / Published online: 18 May 2020 © The Author(s) 2020. This article is published with open access Abstract The lysyl oxidase (LOX) family is closely related to the progression of glioma. To ensure the clinical signiﬁcance of LOX family in glioma, The Cancer Genome Atlas (TCGA) database was mined and the analysis indicated that higher LOXL1 expression was correlated with more malignant glioma progression. The functions of LOXL1 in promoting glioma cell survival and inhibiting apoptosis were studied by gain- and loss-of-function experiments in cells and animals. LOXL1 was found to exhibit antiapoptotic activity by interacting with multiple antiapoptosis modulators, especially BAG family molecular chaperone regulator 2 (BAG2). LOXL1-D515 interacted with BAG2-K186 through a hydrogen bond, and its lysyl 1234567890();,: 1234567890();,: oxidase activity prevented BAG2 degradation by competing with K186 ubiquitylation. Then, we discovered that LOXL1 expression was speciﬁcally upregulated through the VEGFR-Src-CEBPA axis. Clinically, the patients with higher LOXL1 levels in their blood had much more abundant BAG2 protein levels in glioma tissues. Conclusively, LOXL1 functions as an important mediator that increases the antiapoptotic capacity of tumor cells, and approaches targeting LOXL1 represent a potential strategy for treating glioma.
[Show full text]
Matrix Stiffness-Upregulated LOXL2 Promotes Fibronectin Production
Wu et al. Journal of Experimental & Clinical Cancer Research (2018) 37:99 https://doi.org/10.1186/s13046-018-0761-z RESEARCH Open Access Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation Sifan Wu1, Qiongdan Zheng1, Xiaoxia Xing1, Yinying Dong1, Yaohui Wang2, Yang You1, Rongxin Chen1, Chao Hu3, Jie Chen1, Dongmei Gao1, Yan Zhao1, Zhiming Wang4, Tongchun Xue1, Zhenggang Ren1 and Jiefeng Cui1* Abstract Background: Higher matrix stiffness affects biological behavior of tumor cells, regulates tumor-associated gene/ miRNA expression and stemness characteristic, and contributes to tumor invasion and metastasis. However, the linkage between higher matrix stiffness and pre-metastatic niche in hepatocellular carcinoma (HCC) is still largely unknown. Methods: We comparatively analyzed the expressions of LOX family members in HCC cells grown on different stiffness substrates, and speculated that the secreted LOXL2 may mediate the linkage between higher matrix stiffness and pre- metastatic niche. Subsequently, we investigated the underlying molecular mechanism by which matrix stiffness induced LOXL2 expression in HCC cells, and explored the effects of LOXL2 on pre-metastatic niche formation, such as BMCs recruitment, fibronectin production, MMPs and CXCL12 expression, cell adhesion, etc. Results: Higher matrix stiffness significantly upregulated LOXL2 expression in HCC cells, and activated JNK/c-JUN signaling pathway. Knockdown of integrin β1andα5 suppressed LOXL2 expression and reversed the activation of above signaling pathway. Additionally, JNK inhibitor attenuated the expressions of p-JNK, p-c-JUN, c-JUN and LOXL2, and shRNA-c-JUN also decreased LOXL2 expression. CM-LV-LOXL2-OE and rhLOXL2 upregulated MMP9 expression and fibronectin production obviously in lung fibroblasts.
[Show full text]
Prognostic Significance of Abnormal Matrix Collagen Remodeling in Colorectal Cancer Based on Histologic and Bioinformatics Analysis
ONCOLOGY REPORTS 44: 1671-1685, 2020 Prognostic significance of abnormal matrix collagen remodeling in colorectal cancer based on histologic and bioinformatics analysis YUQI LIANG1,2, ZHIHAO LV3, GUOHANG HUANG4, JINGCHUN QIN1,2, HUIXUAN LI1,2, FEIFEI NONG1,2 and BIN WEN1,2 1Department of Science and Technology Innovation Center, Guangzhou University of Chinese Medicine; 2Department of PI-WEI Institute of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510000; 3Department of Anorectal Surgery, Zhongshan Hospital Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, Guangdong 528400; 4Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, SAR 999077, P.R. China Received February 25, 2020; Accepted July 20, 2020 DOI: 10.3892/or.2020.7729 Abstract. As the major component of the tumor matrix, CRC. Furthermore, the results of Gene Ontology (GO) and collagen greatly influences tumor invasion and prognosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis The present study compared the remodeling of collagen and suggest that collagen may promote tumor development by collagenase in 56 patients with colorectal cancer (CRC) using activating platelets. Collectively, the abnormal collagen Sirius red stain and immunohistochemistry, exploring the remodeling, including associated protein and coding genes is relationship between collagen remodeling and the prognosis associated with the tumorigenesis and metastasis, affecting the of CRC. Weak or strong changes in collagen fiber arrange- prognosis of patients with CRC. ment in birefringence were observed. With the exception of a higher density, weak changes equated to a similar Introduction arrangement in normal collagen, while strong changes facilitated cross-linking into bundles. Compared with normal Colorectal cancer (CRC) has a high global incidence and tissues, collagen I (COL I) and III (COL III) deposition was mortality rate (1).
[Show full text]
Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression
www.nature.com/scientificreports OPEN Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression in Pancreatic Cancer Received: 3 April 2018 Nobutake Tanaka1, Suguru Yamada1, Fuminori Sonohara1, Masaya Suenaga1, Masamichi Accepted: 19 June 2018 Hayashi1, Hideki Takami1, Yukiko Niwa1, Norifumi Hattori1, Naoki Iwata1, Mitsuro Kanda1, Published: xx xx xxxx Chie Tanaka1, Daisuke Kobayashi1, Goro Nakayama1, Masahiko Koike1, Michitaka Fujiwara1, Tsutomu Fujii2 & Yasuhiro Kodera1 Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2 (LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial-to-mesenchymal transition (EMT) in various cancers. This study aimed to explore the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the context of EMT status. LOX family mRNA expression was measured in PC cell lines, and LOXL2 protein levels were examined in surgical specimens resected from 170 patients with PC. Higher LOXL2 expression was observed in cell lines from mesenchymal type PC than in those from epithelial type PC. A signifcant correlation between LOXL2 expression and the EMT status defned based on the expression of E-cadherin and vimentin was observed in surgical specimens (P < 0.01). The disease-free survival and overall survival rates among patients with low LOXL2 expression were signifcantly better than those among patients with high LOXL2 expression (P < 0.001). According to the multivariate analysis, high LOXL2 expression (P = 0.03) was a signifcant independent prognostic factor for patients with PC. Additionally, LOX inhibition signifcantly decreased PC cell proliferation, migration, and invasion in vitro. In conclusion, LOXL2 expression is potentially associated with PC progression, and LOXL2 expression represents a biomarker for predicting the prognosis of patients with PC who have undergone complete resection.
[Show full text]
LOXL2-Mediated H3K4 Oxidation Reduces Chromatin Accessibility in Triple-Negative Breast Cancer Cells
Oncogene (2020) 39:79–121 https://doi.org/10.1038/s41388-019-0969-1 ARTICLE LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells 1 1 2 1 1 1 J. P. Cebrià-Costa ● L. Pascual-Reguant ● A. Gonzalez-Perez ● G. Serra-Bardenys ● J. Querol ● M. Cosín ● 1,3 4 4 2 5 6 G. Verde ● R. A. Cigliano ● W. Sanseverino ● S. Segura-Bayona ● A. Iturbide ● D. Andreu ● 1 1,7 1 1,7,8,9 10 6,10 P. Nuciforo ● C. Bernado-Morales ● V. Rodilla ● J. Arribas ● J. Yelamos ● A. Garcia de Herreros ● 2 1 T. H. Stracker ● S. Peiró Received: 28 January 2019 / Revised: 8 July 2019 / Accepted: 9 August 2019 / Published online: 28 August 2019 © The Author(s) 2019. This article is published with open access Abstract Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modiﬁcation with an unknown physiological function. We ﬁnd that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels 1234567890();,: 1234567890();,: and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy.
[Show full text]
Inhibition of Lysyl Oxidase Like-2 (LOXL2) Reduces Cardiac Interstitial Fibrosis in Mice
Inhibition of Lysyl Oxidase Like-2 (LOXL2) reduces cardiac interstitial fibrosis in mice A Buson,B LLC Cao, M MD Deodhar, dh ADFiA D Findlay, dl JSFJ S Foot, t AGA Greco, WJW Jarolimek, li k J MLPBR*Moses, L Perryman, B Rayner*, HHCS C Schilter, hilt X XT Tan, CITC I Turner, T T Yow, A Zahoor, W Zhou Drug Discovery, Pharmaxis Ltd., 20 Rodborough Road, Frenchs Forest, NSW, Australia; *Heart Research Institute, Eliza Street, Newton, NSW, Australia Introduction Lysyl oxidases are a family of enzymes Experimental protocol Cmpd A improves cardiac function responsible for the conversion of the primary EExpExperimentalperiimentltal ProtocolPProtot coll amine group of (hydroxyl-) lysine residues to the MI/Sham corresponding aldehyde. In extracellular matrix A 100 proteins, lysyl oxidases contribute to cross-linking, Monitoring survival rate thereby stabilising areas of fibrosis that occur 80 following tissue injury. Accumulation of cross- ** 60 linked extracellular matrix and the resulting excessive fibrosis can ultimately progress to organ Echocardiography at 24 hrs and 28 days post-MI 40 failure. Daily oral gavage for 28 days Heart photography 20 Yan et al (DOI: 10.1038/ncomms13710) have PBS Heart weight/body weight Ejection Fraction [%] 0 recently shown that an enzyme that crosslinks Cmpd A: 25 mg/kg, once a day Masson trichrome stain AM dA collagen—Lysyl Oxidase-Like-2 (LOXL2)—is Losartan (LOS): 15 mg/kg, once a day H LOS S +PBS mp + I C essential for interstitial fibrosis and mechanical M MI Sham group: No treatment B + dysfunction of pathologically stressed hearts, with MI other lysyl oxidase family members less This model was performed by CL Laboratory, LLC, Baltimore, MD.
[Show full text]
Emerging Therapies in Primary Sclerosing Cholangitis: Pathophysiological Basis and Clinical Opportunities
J Gastroenterol (2020) 55:588–614 https://doi.org/10.1007/s00535-020-01681-z REVIEW Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities 1,2 1,3,4 Mette Vesterhus • Tom Hemming Karlsen Received: 19 January 2020 / Accepted: 5 March 2020 / Published online: 28 March 2020 Ó The Author(s) 2020 Abstract Primary sclerosing cholangitis (PSC) is a pro- Here, in light of pathophysiology, we outline and critically gressive liver disease, histologically characterized by evaluate emerging treatment strategies in PSC, as tested in inflammation and fibrosis of the bile ducts, and clinically recent or ongoing phase II and III trials, stratified per a leading to multi-focal biliary strictures and with time cir- triad of targets of nuclear and membrane receptors regu- rhosis and liver failure. Patients bear a significant risk of lating bile acid metabolism, immune modulators, and cholangiocarcinoma and colorectal cancer, and frequently effects on the gut microbiome. Furthermore, we revisit the have concomitant inflammatory bowel disease and UDCA trials of the past and critically discuss relevant autoimmune disease manifestations. To date, no medical aspects of clinical trial design, including how the choice of therapy has proven significant impact on clinical outcomes endpoints, alkaline phosphatase in particular, may affect and most patients ultimately need liver transplantation. the future path to novel, effective PSC therapeutics. Several treatment strategies have failed in the past and whilst prescription of ursodeoxycholic acid (UDCA) pre- Keywords Primary sclerosing cholangitis Á Therapy Á vails, controversy regarding benefits remains. Lack of Study design Á Alkaline phosphatase statistical power, slow and variable disease progression, lack of surrogate biomarkers for disease severity and other Abbreviations challenges in trial design serve as critical obstacles in the AE2 Chloride/bicarbonate anion exchanger type 2 development of effective therapy.
[Show full text]
LOXL3-Sv2, a Novel Variant of Human Lysyl Oxidase-Like 3 (LOXL3), Functions As an Amine Oxidase
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 39: 719-724, 2017 LOXL3-sv2, a novel variant of human lysyl oxidase-like 3 (LOXL3), functions as an amine oxidase CHANKYU JEONG and YOUNGHO KIM Department of Biochemistry, Wonkwang University School of Medicine, Institute of Wonkwang Medical Science, Iksan, Jeonbuk 570-749, Republic of Korea Received May 23, 2016; Accepted January 13, 2017 DOI: 10.3892/ijmm.2017.2862 Abstract. Human lysyl oxidase-like 3 (LOXL3) functions paralogues (LOX, LOXL, LOXL2, LOXL3 and LOXL4) as a copper-dependent amine oxidase toward collagen and contain a copper-binding domain, residues for lysyl-tyrosyl elastin. The LOXL3 protein contains four scavenger receptor quinone (LTQ) and a cytokine receptor-like (CRL) domain cysteine-rich (SRCR) domains in the N-terminus in addi- in the C-terminus. In addition, four repeated copies of scav- tion to the C-terminal characteristic domains of the lysyl enger receptor cysteine-rich (SRCR) domains are found in the oxidase (LOX) family, such as a copper-binding domain, a N-terminus of only LOXL2, LOXL3 and LOXL4, suggesting cytokine receptor-like domain and residues for the lysyl-tyrosyl novel functional roles assigned to these three members (4-6). quinone cofactor. Using BLASTN searches, we identified a LOXL3 has been reported to be associated with a diverse novel variant of LOXL3 (termed LOXL3-sv2), which lacked range of diseases in both humans and animals. LOXL3 was the sequences corresponding to exons 4 and 5 of LOXL3. The reported to interact with Snail to downregulate the expression LOXL3-sv2 mRNA is at least 2,398 bp in length, encoding a of E-cadherin in carcinoma progression (7), to induce the 608 amino acid-long polypeptide with a calculated molecular autophagy of chondrocytes in osteoarthritis (8) and to play an mass of 67.4 kDa.
[Show full text]
Linking LOXL2 to Cardiac Interstitial Fibrosis
International Journal of Molecular Sciences Review Linking LOXL2 to Cardiac Interstitial Fibrosis Melisse Erasmus 1,2 , Ebrahim Samodien 1 , Sandrine Lecour 3 , Martin Cour 4 , Oscar Lorenzo 5,6 , Phiwayinkosi Dludla 1 , Carmen Pheiffer 1,2 and Rabia Johnson 1,2,* 1 Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7501, South Africa; [email protected] (M.E.); [email protected] (E.S.); [email protected] (P.D.); carmen.pheiff[email protected] (C.P.) 2 Department of Medical Physiology, Stellenbosch University, Cape Town 7505, South Africa 3 Hatter Institute for Cardiovascular Research in Africa (HICRA), University of Cape Town, Cape Town 7925, South Africa; [email protected] 4 Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Médecine Intensive-Réanimation, Place d’Arsonval, 69437 Lyon, France; [email protected] 5 Institute de Investigación Sanitaria-FJD, Faculty of Medicine, University Autónoma de Madrid, 28049 Madrid, Spain; [email protected] 6 Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Network, 28040 Madrid, Spain * Correspondence: [email protected] Received: 8 July 2020; Accepted: 29 July 2020; Published: 18 August 2020 Abstract: Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension. These factors can affect gene expression through epigenetic modifications.
[Show full text]
Mir-29A Is Repressed by MYC in Pancreatic Cancer and Its Restoration Drives Tumor-Suppressive Effects Via Downregulation of LOXL2 Shatovisha Dey1, Jason J
Published OnlineFirst October 29, 2019; DOI: 10.1158/1541-7786.MCR-19-0594 MOLECULAR CANCER RESEARCH | RNA BIOLOGY miR-29a Is Repressed by MYC in Pancreatic Cancer and Its Restoration Drives Tumor-Suppressive Effects via Downregulation of LOXL2 Shatovisha Dey1, Jason J. Kwon1, Sheng Liu1, Gabriel A. Hodge1, Solaema Taleb1, Teresa A. Zimmers2,3, Jun Wan1,2, and Janaiah Kota1,2 ABSTRACT ◥ Pancreatic ductal adenocarcinoma (PDAC) is an intractable Implications: This study unravels a novel functional role of miR-29a cancer with a dismal prognosis. miR-29a is commonly downregu- in PDAC pathogenesis and identifies an MYC–miR-29a–LOXL2 axis lated in PDAC; however, mechanisms for its loss and role still remain in regulation of the disease progression, implicating miR-29a as a unclear. Here, we show that in PDAC, repression of miR-29a is potential therapeutic target for PDAC. directly mediated by MYC via promoter activity. RNA sequencing analysis, integrated with miRNA target prediction, identified global Visual Overview: http://mcr.aacrjournals.org/content/molcanres/ miR-29a downstream targets in PDAC. Target enrichment coupled 18/2/311/F1.large.jpg. with gene ontology and survival correlation analyses identified the top five miR-29a–downregulated target genes (LOXL2, MYBL2, CLDN1, HGK,andNRAS) that are known to promote tumorigenic mechanisms. Functional validation confirmed that upregulation of miR-29a is sufficient to ablate translational expression of these five genes in PDAC. We show that the most promising target among the identified genes, LOXL2, is repressed by miR-29a via 30-untranslated region binding. Pancreatic tissues from a PDAC murine model and patient biopsies showed overall high LOXL2 expression with inverse correlations with miR-29a levels.
[Show full text]