Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo

Tian，Li1; Huang，Yongyi1; Zhang，Baozhen2; Song，Yi1; Yang，Lin3; Chen，Qianqian1; Wang，Zheng3; Wang，Yiling1; He，Qihan1; Yang，Wenhan1; Yu，Shuyong4; Lu，Tianyu5; Liu，Zichen1; Gao，Kaiping1; Fan，Xiujun2; Song，Jian4; Zhai，Rihong1

2023

10.32604/or.2023.028791

Oncology Research   Impact Factor & Quartile

0965-0407

1555-3906

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 challenge. By RNA-sequencing analysis, we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA. LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion. Silencing of LLNLR-299G3.1 with ASO (antisense oligonucleotide) resulted in opposite effects. Mechanistically, LLNLR-299G3.1 bound to cancer-associated RNA binding proteins and regulated the expression of cancer-related genes, including OSM, TNFRSF4, HRH3, and SSTR3. ChIRP-seq (chromatin isolation by RNA purification and sequencing) revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1. Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4. Therapeutically, 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 vivo. Overall, 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.

Antisense oligonucleotide (ASO) Chromatin Esophageal squamous cell carcinoma (ESCC) LLNLR-299G3.1 Placental chondroitin sulfate A binding peptide (plCSA-BP)-coated nanoparticles

SCI

English

Others

Natural Science Foundation of Guangdong Province[2022A1515012033];National Natural Science Foundation of China[81571445];National Natural Science Foundation of China[81572908];

Oncology

Oncology

WOS:001038506600005

TECH SCIENCE PRESS

CLINICAL MEDICINE

2-s2.0-85163680576

Scopus

1.School of Public Health,International Cancer Center,Guangdong Key Laboratory for Genome Stability & Disease Prevention,Shenzhen University Medical School,Shenzhen,China
2.Shenzhen Institute of Advanced Technology,Chinese Academy of Science,Shenzhen,China
3.Department of Thoracic Surgery,Shenzhen People’s Hospital,Shenzhen,China
4.Department of Gastroenterology,Hainan Tumor Hospital,Haikou,China
5.Department of Gastroenterology,Southern University of Science and Technology Hospital,Shenzhen,China

Tian，Li,Huang，Yongyi,Zhang，Baozhen,et al. Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo[J]. Oncology Research,2023,31(4):463-479.

Tian，Li.,Huang，Yongyi.,Zhang，Baozhen.,Song，Yi.,Yang，Lin.,...&Zhai，Rihong.(2023).Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo.Oncology Research,31(4),463-479.

Tian，Li,et al."Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo".Oncology Research 31.4(2023):463-479.