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Long non-coding RNA AFAP1-AS1 plays an oncogenic role in promoting cell migration in non-small cell lung cancer

  • Juan He
  • Ke Wu
  • Chenglin Guo
  • Jian-Kang Zhou
  • Wenchen Pu
  • Yulan Deng
  • Yuanli Zuo
  • Yun Zhao
  • Lunxu Liu
  • Yu-Quan Wei
  • Yong Peng
Original Article
  • 135 Downloads

Abstract

Long non-coding RNA (lncRNA) plays an important role in tumor progression and metastasis. Emerging evidence indicates that lncRNA actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) is dysregulated in certain tumors. However, the function of AFAP1-AS1 in non-small cell lung cancer (NSCLC) remains elusive. In this study, we conducted global lncRNA profiling and identified that AFAP1-AS1 is significantly upregulated in NSCLC, suggesting that AFAP1-AS1 may be important for lung cancer development. For the first time, the transcription initiation and termination sites of AFAP1-AS1 were identified by rapid amplification of cDNA ends technology, and the sequencing data indicated that AFAP1-AS1 in lung cancer cells is a novel transcript variant. Through gain- and loss-of-function studies, AFAP1-AS1 was demonstrated to promote cell migration and invasion. Mechanistically, AFAP1-AS1 functions through positively regulating the expression of AFAP1 protein. On the other hand, the expression of lncRNA AFAP1-AS1 negatively correlates with CpG methylation status of its gene promoter, identified in both lung cancer cells and patient tissues, and treatment with DNA methyltransferase inhibitor decitabine significantly activates AFAP1-AS1 expression, strongly supporting that AFAP1-AS1 expression is tightly regulated by DNA methylation. Taken together, this study demonstrates that AFAP1-AS1 acts as an oncogene in NSCLC to promote cell migration partly by upregulating AFAP1 expression, while its own expression is controlled by DNA methylation, and highlights its diagnostic and therapeutic values for NSCLC patients.

Keywords

Lung cancer AFAP1-AS1 AFAP1 Cell migration Cell invasion DNA methylation 

Abbreviations

NSCLC

Non-small cell lung carcinoma

lncRNA

Long non-coding RNA

AFAP1-AS1

Actin filament-associated protein 1-antisense RNA 1

AFAP1

Actin filament-associated protein 1

RACE

Rapid amplification of cDNA ends

TSS

Transcription start site

TCGA

The Cancer Genome Atlas

GEO

Gene Expression Omnibus

GO

Gene ontology

KEGG

Kyoto encyclopedia of genes and genomes

FISH

RNA fluorescence in situ hybridization

Notes

Acknowledgements

This work was supported by National Key R&D Program of China (2016YFA0502204 and 2017YFA0504304), and National Natural Science Foundation of China (81772960 and 81572739).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

18_2018_2923_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 24 kb)

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
  2. 2.College of Life SciencesSichuan UniversityChengduChina

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