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Targeting LncRNA llnlr-299g3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo

引用

Oncology Research 2023年第4期31卷 463-479页

作者： LI TIAN YONgYI HUANg BAOZHEN ZHANg YI SONg LIN YANg QIANQIAN CHEN ZHENg WANg YILINg WANg QIHAN HE WENHAN YANg SHUYONg YU TIANYU LU ZICHEN LIU KAIPINg gAO XIUJUN FAN JIAN SONg RIHONg ZHAI School of Public Health International Cancer CenterGuangdong Key Laboratory for Genome Stability&Disease PreventionShenzhen University Medical SchoolShenzhenChina Shenzhen Institute of Advanced Technology Chinese Academy of ScienceShenzhenChina Department of Thoracic Surgery Shenzhen People’s HospitalShenzhenChina Department of gastroenterology Hainan Tumor HospitalHaikouChina Department of gastroenterology Southern University of Science and Technology HospitalShenzhenChina

Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a *** RNA-sequencing analysis,we identified that llnlr-299g3.1 was a novel ESCC-associated ***-299g3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and *** of llnlr-299g3.1 with ASO(antisense oligonucleotide)resulted in opposite ***,llnlr-299g3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and ***-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for *** experiments confirmed that the effects of llnlr-299g3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and ***,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in ***,our results suggest that llnlr-299g3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.

关键词： llnlr-299g3.1 Chromatin Esophageal squamous cell carcinoma(ESCC) Antisense oligonucleotide(ASO) Placental chondroitin sulfate A binding peptide(plCSA-BP)-coated nanoparticles

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