Hox Genes in Adult Tissues and Their Role in Endothelial Cell Differentiation and Angiogenesis

Nova-Lamperti, Estefanía; Aguilera, Valeria; Oporto, Katherine; PaulaGuzmán,; Ormazábal, Valeska; Zúñiga, Felipe; Escudero, Carlos; Aguayo, Claudio

doi:10.5772/intechopen.76745

Cited by 10 publications

(9 citation statements)

References 90 publications

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“…These results also matched with the study done by Bruhl et al (32) , Nova-Lampeti et al (33) , who reported that HOXA9 regulates angiogenesis and stimulate endothelial cell migration and documented that HOXA9 has a precise role in migration of endothelial cells without affecting other processes such as cell cycle/division.…”

Section: Discussionsupporting

confidence: 91%

Expression of Homeobox A9 (HOXA9) in Non- Melanoma Skin Cancer: A Clinical and Immunohistochemical study

Salama

Shoeib

Shehata

et al. 2021

The Egyptian Journal of Hospital Medicine

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Background: Homeobox A9 (HOXA9) has been implicated in acute myeloid leukemia and cancer breast but, little is known about HOXA9 expression in non-melanoma skin cancer (NMSC); basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Objective: The aim of the current work was to study HOXA9 expression in NMSC by immunohistochemical method. Patients and Methods: This case-control study included a total of 45 cases with NMSC; 15 BCC and 30 SCC beside 45 age and sex-matched normal apparently healthy controls, selected from Dermatology, Andrology & Sexually transmitted diseases (STDs) Outpatient Clinic, Menoufia University Hospital, during the period December 2018 to June 2020. Clinical evaluation and histopathological evaluation confirmed the diagnosis of SCC and BCC. Results: Expression of HOXA9 in the overlying epidermis was positive in 83.3% of SCC cases with strong intensity in 68% and nucleocytoplasmic localization in 100%. HOXA9 was positive in 60% of BCC cases with mild intensity in 77.8% and nucleocytoplasmic localization in 100%. In control sections, HOXA9 was in all sections (100%) with strong intensity in 77.8%, and nucleocytoplasmic localization in all of them 100%. Regarding tumor islands; expression of HOXA9 was positive in 26 (86.7%) cases of SCC and was positive in 2 (13.3%) of BCC cases. There was significant higher HOXA9 H-score in control skin than NMSC (p<0.001). Conclusions: It could be concluded that HOXA9 may be implicated in pathogenesis and may represent a target therapy for NMSC.

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Section: Discussionsupporting

confidence: 91%

Expression of Homeobox A9 (HOXA9) in Non- Melanoma Skin Cancer: A Clinical and Immunohistochemical study

Salama

Shoeib

Shehata

et al. 2021

The Egyptian Journal of Hospital Medicine

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“…The upregulated genes were involved in functional categories related to the type I interferon (IFN) signaling pathway, virus response, ATP response, purine nucleoside metabolism, and negative regulation of cell proliferation. Among these, we identified CTBP2 , MXI1 , CLMN , IFIT3 , IFITM1 , PTEN , PTK2B , SSTR5 , SPRY1 , and the known factors implicated in VEGF pathways, such as LEPR ( 87 ), HIF3A (GO identifier, 0001944), PTEN ( 88 ), LRG1 ( 82 ), MDK ( 89 ) (GO identifier, 0001944), and HOXA1 ( 90 ). On the other hand, downregulated genes were centered on categories related to cell adhesion, circadian rhythm, extracellular matrix (ECM) organization, negative regulation of DNA binding transcription factor activity, negative regulation of blood coagulation, and response to cyclic AMP (cAMP).…”

Section: Resultsmentioning

confidence: 99%

Genomic Landscapes of Noncoding RNAs Regulating VEGFA and VEGFC Expression in Endothelial Cells

Mushimiyimana

Bosch

Niskanen

et al. 2021

Molecular and Cellular Biology

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Vascular endothelial growth factors (VEGFs) are best known as key regulators of angiogenesis and lymphangiogenesis. Although VEGFs have been promising therapeutic targets for various cardiovascular related diseases, their regulatory landscape in endothelial cells remains elusive. Several studies have highlighted the involvement of non-coding RNAs (ncRNAs) in the modulation of VEGF expression. In this study, we investigated the role of two classes of non-coding RNAs, long ncRNA (lncRNA) and enhancer RNAs (eRNAs), in the transcriptional regulation of VEGFA and VEGFC. By integrating genome-wide global run-on (GRO-seq) and Hi-C data, we identified putative lncRNAs and eRNAs associated with VEGFA and VEGFC genes in endothelial cells. A subset of the identified putative enhancers demonstrated regulatory activity in a reporter assay. Importantly, we demonstrate that deletion of enhancers and lncRNAs by CRISPR/Cas9 promoted significant changes in VEGFA and VEGFC expression. RNA-seq data from lncRNA deletions showed downstream factors implicated in VEGFA and VEGFC linked pathways, such as angiogenesis and lymphangiogenesis, suggesting functional roles for these lncRNAs. Our study uncovers novel lncRNAs and eRNAs regulating VEGFA and VEGFC that can be targeted to modulate the expression of these important molecules in endothelial cells.

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“…Homeobox proteins encode transcription factors controlling embryonic development, and regulate the proliferation and differentiation of cells throughout the reproductive cycle. It has also been stated that they play critical roles in the growth and development of the endometrium together with estrogen and progesterone hormones that regulate endometrial physiology (26).…”

Section: Discussionmentioning

confidence: 99%

Immunolocalization of Hoxa11 and HLX Proteins in Cow Placenta During Pregnancy

Topaloğlu¹,

Ketani²,

Aakbalink³

et al. 2022

SVR

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In addition to its many functions, the placenta is characterized by the intensity and characteristics of its hormonal functions. It has been reported that the development and vascularization of the placenta with normal fetal growth is regulated by many factors such as growth factors, transcriptional factors, and homeobox proteins. This study was conducted to determine the distribution and possible physiological roles of HOXA11 and HLX in the uterus and placenta of pregnant cows. In this study, 27 pregnant Holstein breed cow uteri and placentas obtained from private slaughterhouses were used as tissue samples. In order to determine the pregnancy period of the obtained uterus, the ages of the fetuses were calculated according to the age calculation formula. The uteri were classified under three different groups as the first (69-89 days), second (99-178 days), and third (190-269 days) periods of pregnancy so that there are 9 animals in each group. Tissue samples were then subjected to immunohistochemistry to demonstrate the presence of HOXA11 and HLX proteins. It was observed that HOXA11 and HLX immunoreactions occurred prominently in the luminal and glandular epithelial cells of the uterus during pregnancy, and the maternal epithelial cells of the placenta and UTC and TGC/BNCs. In addition, it was determined that HOXA11 immunoreaction also formed in some vascular endothelial cells. Immunohistochemical findings in this study suggested that Hoxa11 and HLX may affect the proliferation and differentiation of cells in the uterus and placenta during pregnancy in cows, and that these proteins may contribute to normal uterine physiology, placentation formation, and continuity of pregnancy in cows.Key words: Hox proteins; HOXA11; HLX; placentaIMUNOLOKALIZACIJA PROTEINOV HOXA11 IN HLX V POSTELJICI KRAVE MED BREJOSTJOIzvleček: Za posteljico so poleg številnih funkcij značilne intenzivnost in karakteristike njenih hormonskih funkcij. Poročali so,da razvoj in ožiljenost posteljice pri normalni rasti ploda uravnavajo številni dejavniki, kot so rastni dejavniki, transkripcijski djavniki in homeoboks proteini. Ta študija je bila izvedena z namenom določiti porazdelitev in morebitno fiziološko vlogo protnov HOXA11 in HLX v maternici in posteljici brejih krav. Za vzorce tkiv smo uporabili maternice in posteljice 27 krav pasem Holstein, pridobljenih v zasebnih klavnicah. Obdobje brejosti smo izračunali na podlagi starosti plodov po formuli. Maternice smoglede na obdobje brejosti uvrstili v tri skupine po 9 vzorcev: 1 (69-89 dni), 2 (99-178 dni) in 3 (190-269 dni). Prisotnost proteinoHOXA11 in HLX v vzorcih tkiv smo preverili z imunohistokemijo. Proteini HOXA11 in HLX so bili prisotni predvsem v luminalnihin žleznih epitelijskih celicah maternice ter v epitelijskih celicah maternalne posteljice, UTC in TGC/BNC. Prisotnost HOXA1je bila zaznavna tudi v nekaterih žilnih endotelijskih celicah. Rezultati imunohistokemije v tej študiji kažejo na morebiten vplivproteinov HOXA11 in HLX na proliferacijo in diferenciacijo celic v maternici in posteljici krav med brejostjo in na morebitno vlogoteh proteinov pri normalni fiziologiji maternice, nastanku posteljice in vztrajanju brejosti pri kravah.Ključne besede: proteini Hox; HOXA11; HLX; posteljica

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Hox Genes in Adult Tissues and Their Role in Endothelial Cell Differentiation and Angiogenesis

Cited by 10 publications

References 90 publications

Expression of Homeobox A9 (HOXA9) in Non- Melanoma Skin Cancer: A Clinical and Immunohistochemical study

Expression of Homeobox A9 (HOXA9) in Non- Melanoma Skin Cancer: A Clinical and Immunohistochemical study

Genomic Landscapes of Noncoding RNAs Regulating VEGFA and VEGFC Expression in Endothelial Cells

Immunolocalization of Hoxa11 and HLX Proteins in Cow Placenta During Pregnancy

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