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

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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.

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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

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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).

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Author notes

  1. Juan He, Ke Wu and Chenglin Guo equally contributed to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Renmin South Road, Section 3-17, Chengdu, 610041, China

    Juan He, Ke Wu, Chenglin Guo, Jian-Kang Zhou, Wenchen Pu, Yulan Deng, Lunxu Liu, Yu-Quan Wei & Yong Peng

  2. College of Life Sciences, Sichuan University, Chengdu, 610064, China

    Yuanli Zuo & Yun Zhao

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  1. Juan He
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Correspondence to Yong Peng.

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He, J., Wu, K., Guo, C. et al. Long non-coding RNA AFAP1-AS1 plays an oncogenic role in promoting cell migration in non-small cell lung cancer. Cell. Mol. Life Sci. 75, 4667–4681 (2018). https://doi.org/10.1007/s00018-018-2923-8

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