CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

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外文摘要：Aberrant expression of circular RNAs(circRNAs)is frequently linked to colorectal cancer(CRC).Here,we identified circZFR as a promising biomarker for CRC diagnosis and prognosis,CircZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence,advanced-stages,and metastasis.In both in vitro and in vivo settings,circZFR promoted the growth and spread while suppressing apoptosis of CRC.Exosomes with circZFR overexpression promoted the proliferation and migration of cocultured CRC cells.Mechanistically,epithelial splicing regulatory protein 1(ESRP1)in CRC cells may enhance the production of circZFR.BCL2-associated transcription factor 1(BCLAF1)bound to circZFR,which prevented its ubiquitinated degradation.Additionally,circZFR sponged miR-3127-5p to boost rhotekin 2(RTKN2)expression.Our TCP1-CD-QDs nanocarrier was able to carry and deliver circZFR siRNA(si-circZFR)to the vasculature of CRC tissues and cells,which inhibited the growth of tumors in patient-derived xenograft(PDX)models.Taken together,our results show that circZFR is an oncogenic circRNA,which promotes the development and spread of CRC in a BCLAF1 and miR-3127-5p-dependent manner.CircZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.

外文关键词：

circZFRexosomeESRP1BCLAFImiR-3127-5pnanoparticle(NP)

作者：

Jiaxin Chen、Huijuan Wang、Jianbin Xu、Engeng Chen、Qing Meng、Jiawei Wang、Haoyi Xiang、Wei Zhou、Ge Shan、Zhenyu Ju、Zhangfa Song

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作者单位：

Department of Colorectal Surgery,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China

Key Laboratory of Biological Treatment of Zhejiang Province,Hangzhou 310016,China

Department of Breast Surgery,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China

Department of Orthopedic Surgery,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China

Department of Pulmonary and Critical Care Medicine,Regional medical center for National Institute of Respiratory Disease,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China

Key Laboratory of Regenerative Medicine of Ministry of Education,Institute of Aging and Regenerative Medicine,Jinan University,Guangzhou 510632,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang ProvinceDepartment of Health of Zhejiang ProvinceDepartment of Health of Zhejiang Province

项目编号：

81771502823028993207134981701820LH19H160001LY20H1800142018KY4732018PY025

出版年：

2024

DOI：

10.1007/s11427-023-2514-y

中国科学:生命科学(英文版)

中国科学院

中国科学:生命科学(英文版)

CSTPCD

影响因子：0.806

ISSN：1674-7305

年,卷(期)：2024.67(9)