Cln Three Requiring 9(CTR9),a scaffold protein of the polymerase-associated factor-1(PAF1)complex(PAF1c),is primarily localized in the nucleus of cells.Recent studies show that CTR9 plays essential roles in the development of various human cancers and their occurrence;however,its regulatory roles and precise mechanisms in hepatocellular carcinoma(HCC)remain unclear.In this study,we investigated the roles of CTR9 using in vitro assays and a xenograft mouse model.We found that CTR9 protein is upregulated in tumor tissues from HCC patients.Knockdown of CTR9 substantially reduced HCC cell proliferation,invasion,and migration,whereas its overexpression promoted these activities.In addition,in vitro results revealed that CTR9 silencing dramatically increased cell cycle regulators,p21 and p27,but markedly decreased matrix metalloproteinases,MMP2 and MMP9,with these outcomes reversed upon CTR9 overexpression.Furthermore,the underlying molecular mechanism suggests that CTR9 promoted the oncogene paternally expressed gene 10(PEG10)transcription via its promoter region.Finally,the oncogenic rples of CTR9 were confirmed in a xenograft mouse model.This study confirms that CTR9,an oncoprotein that promotes HCC cell proliferation,invasion,and migration,increases tumor growth in a xenograft mouse model.CTR9 could be a novel therapeutic target.Further investigation is warranted to verify CTR9 potential in novel therapies for HCC.

Bin Zhang;Zhi-yi Liu;Rui Wu;Cheng-ming Zhang;Kuan Cao;Wen-gang Shan;Zhen Liu;Ming Ji;Zi-lu Tian;Gautam Sethi;Heng-liang Shi;Ren-hao Wang

Institute of Digestive Diseases,Xuzhou Medical University,Xuzhou 221004,China;Department of General Surgery,The Affiliated Hospital of Xuzhou Medical University,Xuzhou 221004,China;Department of Pharmacology,Yong Loo Lin School of Medicine,National University of Singapore,Singapore 117600,Singapore;Central Laboratory,The Affiliated Hospital of Xuzhou Medical University,Xuzhou 221004,China

中国药理学报（英文版）

[1]Bin Zhang;Zhi-yi Liu;Rui Wu;Cheng-ming Zhang;Kuan Cao;Wen-gang Shan;Zhen Liu;Ming Ji;Zi-lu Tian;Gautam Sethi;Heng-liang Shi;Ren-hao Wang-.Transcriptional regulator CTR9 promotes hepatocellular carcinoma progression and metastasis via increasing PEG 10 transcriptional activity)[J].中国药理学报（英文版）,2022(08):2109-2118

CTR9,Cln,PAF1c,paternally,rples

Transcriptional,promotes,hepatocellular,carcinoma,progression,metastasis,via,increasing,transcriptional,activity,Three,Requiring,scaffold,polymerase,associated,complex,primarily,localized,nucleus,cells,Recent,studies,show,that,plays,essential,roles,development,various,human,cancers,their,occurrence,however,its,regulatory,precise,mechanisms,HCC,remain,unclear,In,this,study,investigated,using,vitro,assays,xenograft,mouse,model,We,found,upregulated,tumor,tissues,from,patients,Knockdown,substantially,reduced,proliferation,invasion,migration,whereas,overexpression,promoted,these,activities,addition,results,revealed,silencing,dramatically,increased,cycle,regulators,p21,p27,but,markedly,decreased,matrix,metalloproteinases,MMP2,MMP9,outcomes,reversed,upon,Furthermore,underlying,molecular,suggests,oncogene,expressed,PEG10,promoter,region,Finally,oncogenic,were,confirmed,This,confirms,oncoprotein,increases,growth,could,be,novel,therapeutic,target,investigation,warranted,verify,potential,therapies

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