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SK4-OE induced widespread alternative splicing changes and identified 1,639 RASEs enriched in DNA damage/repair, viral processes, translation, and mRNA splicing.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/sk4-potentially-modulates-the-alternative-splicing-profile-associated-with-papillary-thyroid-cancer-development-in-bht101-cells/369553/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/sk4-potentially-modulates-the-alternative-splicing-profile-associated-with-papillary-thyroid-cancer-development-in-bht101-cells/369553.png","ImageObject",300,407,{"name":42,"@type":43},"Quinn Holloway","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How was SK4 studied in papillary thyroid cancer cells?","Question",{"text":63,"@type":64},"SK4 was overexpressed in BHT101 thyroid cancer cells to enable functional and molecular comparison with controls. Cell proliferation and invasion assays assessed behavioral effects.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What molecular analyses were performed to identify SK4 targets?",{"text":68,"@type":64},"Whole-transcriptome sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs). Selected DEGs and RASEs were validated using RT-qPCR.",{"name":70,"@type":61,"acceptedAnswer":71},"What did the study find about alternative splicing changes caused by SK4 overexpression?",{"text":72,"@type":64},"SK4 overexpression globally altered the alternative splicing pattern and identified 1,639 RASEs. RASE genes were enriched in pathways including DNA damage/repair, viral process, translation, and mRNA splicing.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},369553,1790651769,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Submitted 1 August 2024  \nAccepted 8 April 2025  \nPublished 28 May 2025  \nCorresponding author Gong Ye, [21120152@qq.com](21120152@qq.com)  \nAcademic editor Vladimir Uversky  \nAdditional Information and Declarations can be found on page 17  \nDOI 10.7717/peerj.19391  \n Copyright 2025 Wupuer et al.  \nDistributed under  \nCreative Commons CC-BY-NC 4.0  \nOPEN ACCESS  \nSK4 potentially modulates the alternative splicing profile associated with papillary thyroid cancer development in BHT101 cells  \nAlimujiang Wupuer, Xuekelaiti Kuerban and Gong Ye  \nDepartment of Breast and Thyroid Diseases, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China  \nABSTRACT  \nPapillary thyroid cancer (PTC) is an ever-increasing cancer type worldwide, and greatly decreases the life quality and affects survival time of patients during its development and progression, but the underlying mechanisms and key factors for PTC progression are not clear. Recent studies demonstrated the potassium channel protein SK4 participatesin the progression of many cancers, while it lacks the molecular mechanism study for SK4 function. In this study, we performed functional and molecular explorations for SK4 by overexpressing its level in thyroid cancer BHT101 cells. Cellular proliferation and invasion experiments were performed to assess the influences of SK4 on cell behaviors. Further, whole transcriptome sequencing (RNA-seq) analysis helped us systematically investigated the targets of SK4, including differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs), and validated several related DEGs and RASEs by RT-qPCR experiment. In thyroid cancer patients, SK4 expression was completely lost in normal tissues and significantly increased in every stage of tumor tissues compared with normal tissues, which probably results from the low DNA methylation level at its promoter region. Consistent with previous study, SK4 overexpression (SK4-OE) promoted proliferation and invasion ability of BHT10 cells compared with negative control (NC) . By analyzing the RNA-seq data, we detected dozens of DEGs and found that up DEGs were enriched in negative regulation of apoptotic progress, including VTCN1, MSX1, FATE1, TEK, and PRAMEF2 . More importantly, we found SK4-OE globally changed the alternative splicing (AS) pattern and identified 1,639 RASEs. The genes of RASEs were enriched in DNA damage/repair, viral process, translation, and mRNA splicing pathways, which were tightly associated with the pathogenesis and progression of cancers. The splicing regulatory genes from regulated alternative splicing genes (RASGs) could partly explain the reason of global AS dysregulation by SK4-OE in BHT101 cells. Finally, we found the expression of VTCN1, EDN1, SLC29A4, RP11-473M20.16, and CH507-513H4.4 were validated by RT-qPCR, as well as the AS pattern of TMEM116. In summary, we highlight that SK4-regulated AS pattern probably is a novel regulatory mechanism for SK4 in PTC. The identified DEGs and RASEs, as well as SK4 itself, could be used as potential therapeutic targets for PTC treatment in future.  \nSubjects Cell Biology, Genomics, Molecular Biology, Oncology  \nKeywords PTC, SK4, RNA-seq, DEGs, Alternative splicing, DNA damage, Spliceosome  \nHow to cite this article Wupuer A, Kuerban X, Ye G. 2025. SK4 potentially modulates the alternative splicing profile associated with papillary thyroid cancer development in BHT101 cells. PeerJ 13:e19391 [http://doi.org/10.7717/peerj.19391](http://doi.org/10.7717/peerj.19391)  \nINTRODUCTION  \nThyroid cancer, with papillary thyroid cancer (PTC) as the most incident type, is a commonly diagnosed and ever-increasing cancer type worldwide, with 586,000 new cases in 2020, although the survival rate of PTC patients is high (Sung et al., 2021) . Meanwhile, the high incidence of PTC suggests that promising therapeutic techniques and more individualized treatment approach, including molecular targeting therapies, are n","cbCaioW22PquqggF","https://ap.wps.com/l/cbCaioW22PquqggF","pdf",10272787,21,"English","# Abstract\n# Introduction","[{\"question\":\"How was SK4 studied in papillary thyroid cancer cells?\",\"answer\":\"SK4 was overexpressed in BHT101 thyroid cancer cells to enable functional and molecular comparison with controls. Cell proliferation and invasion assays assessed behavioral effects.\"},{\"question\":\"What molecular analyses were performed to identify SK4 targets?\",\"answer\":\"Whole-transcriptome sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs). Selected DEGs and RASEs were validated using RT-qPCR.\"},{\"question\":\"What did the study find about alternative splicing changes caused by SK4 overexpression?\",\"answer\":\"SK4 overexpression globally altered the alternative splicing pattern and identified 1,639 RASEs. RASE genes were enriched in pathways including DNA damage/repair, viral process, translation, and mRNA splicing.\"}]","SK4 potentially modulates the alternative splicing profile associated with papillary thyroid cancer development in BHT101 cells | PDF",1790183388,53]