ELF3-AS1 contributes to gastric cancer progression by binding to hnRNPK and induces thrombocytosis in peripheral blood.

Abstract

Numerous studies have reported that a variety of long noncoding RNAs (lncRNAs) can promote the proliferation, invasion, and migration of different tumor cells. However, different lncRNAs regulate cell functions in various forms, and the exact mechanisms are not clear. Here, we investigated the effect of the lncRNA ELF3-AS1 on gastric cancer (GC) cell function and explored the exact mechanism. Quantitative real-time polymerase chain reaction was used to detect the expression of ELF3-AS1 in GC tissues and adjacent nontumor tissues. Knockdown and overexpression of ELF3-AS1 was used to detect the effect of ELF3-AS1 on cell function. Potential downstream target genes were identified using RNA transcriptome sequencing, while RNA immunoprecipitation, chromatin immunoprecipitation, and Western blotting were performed to explore the tumor promotion mechanisms of ELF3-AS1. We observed that ELF3-AS1 was highly expressed in GC tissues, and high ELF3-AS1 expression predicted poor prognosis. The knockdown of ELF3-AS1 significantly inhibited cell proliferation, migration, and epithelial-mesenchymal transition and promoted apoptosis. Mechanistic investigations revealed that ELF3-AS1 may regulate the downstream target gene, C-C motif chemokine 20, by binding with the RNA-binding protein hnRNPK. Additionally, we found that high ELF3-AS1 expression was associated with thrombocytosis. Interleukin-6 and thrombopoietin may be involved in ELF3-AS1-induced paraneoplastic thrombocytosis. Together, our results demonstrate that aberrantly expressed ELF3-AS1 in GC may play important roles in oncogenesis and progression and is expected to become a new target for the diagnosis and treatment of GC.

• Authors: Shubin Song, Xuezhi He, Jing Wang, Rong Wang, Leilei Wang, Wei Zhao, Yimin Wang, Yongle Zhang, Zhiyong Yu, Dengshun Miao, Yingwei Xue
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 11 Pg. 4553-4569 (Nov 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 34418240 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Chemokine CCL20
• DNA-Binding Proteins
• ELF3 protein, human
• Heterogeneous-Nuclear Ribonucleoprotein K
• Interleukin-6
• Proto-Oncogene Proteins c-ets
• Transcription Factors
• HNRNPK protein, human
• Thrombopoietin

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Chemokine CCL20 (metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• Disease Progression
• Epithelial-Mesenchymal Transition
• Female
• Gene Silencing
• Heterogeneous-Nuclear Ribonucleoprotein K (metabolism)
• Humans
• Interleukin-6 (metabolism)
• Male
• Mice, Nude
• Middle Aged
• Prognosis
• Proto-Oncogene Proteins c-ets (genetics, metabolism)
• Stomach Neoplasms (metabolism, mortality, pathology)
• Thrombocytosis (etiology)
• Thrombopoietin (metabolism)
• Transcription Factors (genetics, metabolism)
• Exome Sequencing
• Mice