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Silencing of Astrocyte Elevated Gene-1 (AEG-1) inhibits the proliferative and invasive potential through interaction with Exostosin-1 (ext-1) in primary and metastatic colon cancer cells

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BIOCELL 2021年第3期45卷 563-576页

作者： SUSHMITHA SRIRAMULU SARUBALA MALAYAPERUMAL SUMAN K.NANDY ANTARA BANERJEE MUSTHAFA M OHAMED ESSA SARAVANABABU CHIDAMBARAM M.WALID QORONFLEH SURAJIT PATHAK Department of Medical Biotechnology Faculty of Allied Health SciencesChettinad Academy of Research and Education(CARE)Chettinad Hospital and Research Institute(CHRI)ChennaiIndia Bioinformatics Centre Department of RDAPNorth-Eastern Hill UniversityTuraIndia Department of Food Science and Nutrition CAMSSultan Qaboos UniversityMuscatOman Ageing and Dementia Research Group Sultan Qaboos UniversityMuscatOman Department of Pharmacology JSS College of PharmacyJSS Academy of Higher Education&ResearchMysuruIndia Research&Policy Department World Innovation Summit for Health(WISH)Qatar FoundationDohaQatar Q3CG Research Institute(QRI) Research&Policy DivisionYpsilantiMI 48917USA

Colon cancer is the third major cause of cancer deaths,accounting for about 8%in terms of mortality *** present study aims to explore the effect of silencing Astrocyte Elevated Gene-1(AEG-1),a metastasis mediating factor,and how it interacts with Exostosin-1(ext-1)protein to inhibit the proliferative and invasive potential in colon cancer *** siRNA transfection was performed using AEG-1 siRNA in SW480 and SW620 colon cancer cell lines,and the expression levels of mRNA and protein were analyzed by Real-time PCR and Immunofluorescence.A simple bioinformatics approach was carried out to identify the possible interactions between AEG-1 and ext-1 using Easy Networks and Pathway Commons *** survival and clonal efficiency were determined using Cell Counting Kit-8 assay and clonogenic assay,apoptosis using flow cytometry analysis,migration and invasion using scratch and Transwell assays,*** siRNA transfection significantly suppressed the expression of AEG-1 in mRNA and protein levels on SW480 and SW620 colon cancer *** our results,we found that ext-1 mRNA and protein level was significantly upregulated in AEG-1 siRNA transfected ***,treatment with AEG-1 siRNA inhibited the proliferation,clonogenic ability,migration,and invasion and also induced *** the bioinformatic approach,our data analyses pointed towards the crosstalk between AEG-1 and ext-1 mediated through Patched-1(PTCH-1)*** current results demonstrated that silencing AEG-1 can restrain cell proliferation,migration,and invasion,ultimately leading to *** AEG-1 siRNA transfected cells,PTCH-1 activity might be modulated by several genes and,in turn,affects the ext-1 ***,these observations not only provide insight into the interplay between AEG-1 and ext-1 but also suggest that AEG-1 may represent a possible candidate therapeutic target through interaction with ext-1 in colon cancer.

关键词： Oncogene ext-1 siRNA Colon cancer AEG-1

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