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

Yu Zhong,Zhaoyang Zeng,Can Guo,Songqing Fan,Fang Xiong,Qianjin Liao,Yong Li,Xiaoling Li,Ming Zhou,Liting Yang,Yujuan Zhou,Guiyuan Li,Yue Tang ,Wei Xiong,Zheng Li,Bo Xiang,Lei Shi,Zhaojian Gong,Yi He,Shanshan Zhang

doi:10.1038/s41392-021-00562-y

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.

Highlights

Lung cancer is the cancer with the highest incidence rate and mortality rate in the world.[1,2] some advances in lung cancer therapy, the five-year overall survival rate remains very low.[3]
A correlation regression analysis showed the AFAP1-AS1 expression was positively correlated with patients’ distant metastasis with lung adenocarcinoma but not in patients with lung squamous carcinoma based on 86 lung adenocarcinoma and 88 lung squamous cell carcinoma patients (Fig. 1c)
AFAP1-AS1 has been reported to be involved in carcinogenesis in a number of types of cancer, including esophagus, adenocarcinoma, gastric cancer, breast cancer, colorectal cancer, nasopharyngeal carcinoma, hepatocellular carcinoma, and non-small lung cancer.[26,42,43,44,45]

Summary

Introduction

Lung cancer is the cancer with the highest incidence rate and mortality rate in the world.[1,2] some advances in lung cancer therapy, the five-year overall survival rate remains very low.[3]. Long noncoding RNAs (lncRNAs) are a class of non-coding RNAs that are more than 200 nucleotides in length without or low protein-coding ability.[5,6,7,8] They contribute to transcriptional, epigenetic, and post-transcriptional regulation through multiple signal pathways, resulting in the occurrence and development of cancer.[9,10,11,12,13,14,15,16,17,18] LncRNAs can function as tumor suppressor- or oncogenes to suppress or activate downstream genes and signaling pathways through competing endogenous RNAs (ceRNAs),[19] interacting with transcription factors or RNA-binding proteins.[20]

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