Please use this identifier to cite or link to this item: http://nuir.lib.nu.ac.th/dspace/handle/123456789/6011
Full metadata record
DC FieldValueLanguage
dc.contributorPreenapan Changphasuken
dc.contributorปรีณาพรรณ ช่างผาสุขth
dc.contributor.advisorWorasak Kaewkongen
dc.contributor.advisorวรศักดิ์ แก้วก่องth
dc.contributor.otherNaresuan Universityen
dc.date.accessioned2024-05-08T02:16:07Z-
dc.date.available2024-05-08T02:16:07Z-
dc.date.created2023en_US
dc.date.issued2023en_US
dc.identifier.urihttp://nuir.lib.nu.ac.th/dspace/handle/123456789/6011-
dc.description.abstractCholangiocarcinoma (CCA) is a cancer that arising from abnormal growth of bile duct epithelium. It is a common cancer among Thai population derived from unhygienic food consumption. Regarding no early-diagnosis and inefficient treatment, therefore, CCA represents very poor prognosis and low survival rate. The molecular mechanisms underlying CCA development are still unclear, however, dysregulation of mRNA splicing is suspected to play a major role as a number of oncogenic aberrant spliced-transcripts in CCA have been reported. Aberrant splicing is caused by the increased activity of Serine/Arginine rich-splicing factors (SRSFs) that translocate into the nucleus as phospho-SRSFs after activated by Serine-arginine protein kinases (SRPKs). In this study, the effects of two SRPK inhibitors (SRPIN340 and SPHINX31) in two CCA cell lines (KKU-213A and TFK-1) were investigated. SRPIN340 and SPHINX31 increased the number of dead cells once stained with calcein-AM/PI as dose-dependent manner. The type of dead cell induction was defined as apoptosis by increasing of apoptotic cell population, diffused cytoplasmic cytochrome c and upregulation of cleaved caspase-3 by Annexin-V/7AAD staining (flow cytometry), immunocytofluorescence and Western blot analysis, respectively. Moreover, Western blot analysis using anti-phospho-epitope of SRSF protein family members revealed lower phospho-SRSFs band intensities for representing the reduction of SRSFs phosphorylation. Particularly, inhibition of nuclear-cytoplasmic translocation of predominant SRSF1 was demonstrated by immunocytofluorescence and Western blotting of subcellular protein fractions. To link these phenotypes with aberrant gene splicing, Bridging Integrator 1 (BIN1) gene was selected. Both SRPIN340 and SPHINX31 can decrease BIN1+12A (oncogenic/anti-apoptotic isoform) once observed by RT-PCR. These results provide the strong evidences that suggests the targeting SRPKs could be an alternative strategy for developing the precise CCA treatment.en
dc.description.abstract-th
dc.language.isoenen_US
dc.publisherNaresuan Universityen_US
dc.rightsNaresuan Universityen_US
dc.subjectApoptosisen
dc.subjectBridging Integrator 1 (BIN1)en
dc.subjectCholangiocarcinoma (CCA)en
dc.subjectSerine/arginine-rich splicing factor (SRSF1)en
dc.subjectSerine-arginine protein kinase (SRPKs)en
dc.subjectSRPK inhibitorsen
dc.subject.classificationBiochemistryen
dc.subject.classificationBiochemistryen
dc.subject.classificationProfessional, scientific and technical activitiesen
dc.subject.classificationMedical diagnostic and treatment technologyen
dc.titleMechanistic insights of SRPK inhibitors in cholangiocarcinoma cell apoptosisen
dc.titleกลไกการทำงานของสารยับยั้งโปรตีนเอสอาร์พีเคที่ส่งเสริมการตายแบบอะพอพโทซิสของเซลล์มะเร็งท่อน้ำดีth
dc.typeThesisen
dc.typeวิทยานิพนธ์th
dc.contributor.coadvisorWorasak Kaewkongen
dc.contributor.coadvisorวรศักดิ์ แก้วก่องth
dc.contributor.emailadvisorworasakk@nu.ac.then_US
dc.contributor.emailcoadvisorworasakk@nu.ac.then_US
dc.description.degreenameMaster of Science (M.S.)en
dc.description.degreenameวิทยาศาสตรมหาบัณฑิต (วท.ม.)th
dc.description.degreelevelMaster's Degreeen
dc.description.degreelevelปริญญาโทth
dc.description.degreedisciplineDepartment of Biochemistryen
dc.description.degreedisciplineภาควิชาชีวเคมีth
Appears in Collections:คณะวิทยาศาสตร์การแพทย์

Files in This Item:
File Description SizeFormat 
PreenapanChangphasuk.pdf9.81 MBAdobe PDFView/Open


Items in NU Digital Repository are protected by copyright, with all rights reserved, unless otherwise indicated.