A SNP-mediated lncRNA (LOC146880) and microRNA (miR-539-5p) interaction and its potential impact on the NSCLC risk.

Abstract

BACKGROUND:

Many cancer-associated single nucleotide polymorphisms (SNPs) are located in the genomic regions of long non-coding RNAs (lncRNAs). Mechanisms of these SNPs in connection to cancer risk are not fully understood.

METHODS:

Association of SNP (rs140618127) in lncRNA LOC146880 with non-small cell lung cancer (NSCLC) was evaluated in a case-control study of 2707 individuals. The mechanism of the SNP's biologic influence was explored with in vitro and in vivo experiments, including plasmid transfection, siRNA knockdown, flow cytometry assessment, and assays of cell proliferation, migration, invasion, and colony formation.

RESULTS:

Association analysis showed that A allele of SNP rs140618127 was associated with low risk of NSCLC in the Chinese population. Lab experiments indicated that SNP rs140618127 contained a binding site for miR-539-5p and the binding between miR-539-5p and LOC146880 resulted in declined phosphorylation of an oncogene, ENO1. The reduced phosphorylation of ENO1 led to decreased phosphorylation of PI3K and Akt, which is further linked to the decline in cell proliferation and tumor progression.

CONCLUSION:

The study demonstrates that SNP rs140618127 in lncRNA loc146880 provides an alternate binding site for microRNA miR-539-5p which affects the phosphorylation of ENO1 and activation of the PI3K and Akt pathway.

• Authors: Tienan Feng, Nannan Feng, Tengteng Zhu, Qiang Li, Qi Zhang, Yu Wang, Ming Gao, Baosen Zhou, Herbert Yu, Min Zheng, Biyun Qian
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 39 Issue 1 Pg. 157 (Aug 14 2020) ISSN: 1756-9966 [Electronic] England
• PMID: 32795333 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• MIRN539 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Tumor Suppressor Proteins
• ENO1 protein, human
• Phosphopyruvate Hydratase

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Case-Control Studies
• Cell Movement
• Cell Proliferation
• DNA-Binding Proteins (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• Middle Aged
• Phosphopyruvate Hydratase (genetics, metabolism)
• Polymorphism, Single Nucleotide
• Prognosis
• RNA, Long Noncoding (genetics)
• Tumor Cells, Cultured
• Tumor Suppressor Proteins (genetics, metabolism)
• Xenograft Model Antitumor Assays