Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc.

Abstract

Actin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients' poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer's migration and invasion may provide novel therapeutic targets for lung cancer patients' early diagnosis and therapy.

• Authors: Yu Zhong, Liting Yang, Fang Xiong, Yi He, Yanyan Tang, Lei Shi, Songqing Fan, Zheng Li, Shanshan Zhang, Zhaojian Gong, Can Guo, Qianjin Liao, Yujuan Zhou, Ming Zhou, Bo Xiang, Xiaoling Li, Yong Li, Zhaoyang Zeng, Guiyuan Li, Wei Xiong
• Journal: Signal transduction and targeted therapy (Signal Transduct Target Ther) Vol. 6 Issue 1 Pg. 240 (06 25 2021) ISSN: 2059-3635 [Electronic] England
• PMID: 34168109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AFAP1-AS1 long noncoding RNA, human
• MYC protein, human
• Proto-Oncogene Proteins c-myc
• RNA, Long Noncoding
• RNA-Binding Proteins
• SNIP1 protein, human
• ZEB1 protein, human
• ZEB2 protein, human
• Zinc Finger E-box Binding Homeobox 2
• Zinc Finger E-box-Binding Homeobox 1

Topics

• A549 Cells
• Animals
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Heterografts
• Humans
• Lung Neoplasms (genetics, pathology)
• Male
• Mice
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Metastasis (genetics, pathology)
• Proto-Oncogene Proteins c-myc (genetics)
• RNA, Long Noncoding (genetics)
• RNA-Binding Proteins (genetics)
• Zinc Finger E-box Binding Homeobox 2 (genetics)
• Zinc Finger E-box-Binding Homeobox 1 (genetics)