Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway

Yu Lian; Fang Xiong; Liting Yang; Hao Bo; Zhaojian Gong; Yumin Wang; Fang Wei; Yanyan Tang; Xiayu Li; Qianjin Liao; Hui Wang; Ming Zhou; Bo Xiang; Xu Wu; Yong Li; Xiaoling Li; Xiang Chen; Guiyuan Li; Can Guo; Zhaoyang Zeng; Wei Xiong

doi:10.1186/s13046-018-0918-9

Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway

J Exp Clin Cancer Res. 2018 Oct 16;37(1):253. doi: 10.1186/s13046-018-0918-9.

Authors

Yu Lian^{1

2

3}, Fang Xiong^{1

3}, Liting Yang^{1

3}, Hao Bo³, Zhaojian Gong³, Yumin Wang³, Fang Wei^{1

3}, Yanyan Tang^{2

4}, Xiayu Li⁵, Qianjin Liao^{2

4}, Hui Wang⁴, Ming Zhou^{1

3}, Bo Xiang^{1

3}, Xu Wu^{2

6}, Yong Li^{2

7}, Xiaoling Li^{1

3}, Xiang Chen¹, Guiyuan Li^{1

3}, Can Guo^{1

3}, Zhaoyang Zeng^{8

9}, Wei Xiong^{10

11}

Affiliations

¹ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Reproductive medicine, Ganzhou Hospital Affiliated to Nanchang University, NanChang, Jiangxi, China.
³ The Key Laboratory of Carcinogenesis and OCancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, Hunan, China.
⁴ Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
⁵ Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁶ Department of Chemistry, University of North Dakota, Grand Forks, North Dakota, USA.
⁷ Department of Cancer Biology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA.
⁸ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China. zengzhaoyang@csu.edu.cn.
⁹ The Key Laboratory of Carcinogenesis and OCancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, Hunan, China. zengzhaoyang@csu.edu.cn.
¹⁰ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China. xiongwei@csu.edu.cn.
¹¹ The Key Laboratory of Carcinogenesis and OCancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, Hunan, China. xiongwei@csu.edu.cn.

Abstract

Background: Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long noncoding RNA, is significantly highly expressed and associated with metastasis and poor prognosis in many cancers, including nasopharyngeal carcinoma (NPC). In this study, we aim to identify the role of AFAP1-AS1 acting as an oncogenic lncRNA to promote NPC metastasis.

Methods: The role of AFAP1-AS1, miR-423-5p, and FOSL2 in NPC metastasis was investigated in vitro and in vivo. Bioinformatics analysis and luciferase activity assays were used to identify the interaction between AFAP1-AS1, miR-423-5p, and FOSL2. Additionally, real-time PCR and western blotting were used to assess the function of AFAP1-AS1 acting as an oncogenic lncRNA to promote NPC progression by regulating miR-423-5p and the downstream Rho/Rac pathway.

Results: In this study, we determined that AFAP1-AS1 functions as a competing endogenous RNA in NPC to regulate the Rho/Rac pathway through miR-423-5p. These interactions can mediate the expression of RAB11B, LASP1, and FOSL2 and accelerate cell migration and invasion via the Rho/Rac signaling pathway or FOSL2. AFAP1-AS1 and FOSL2 could competitively bind with miR-423-5p to regulate several molecules, including RAB11B and LASP1 of the Rho/Rac signaling pathway. AFAP1-AS1 can also regulate the expression of LASP1, which was transcriptionally regulated by FOSL2, resulting in increased migration and invasion of NPC cells via the Rho/Rac signaling pathway.

Conclusions: The observations in this study identify an important role for AFAP1-AS1 as a competing endogenous RNA (ceRNA) in NPC pathogenesis and indicate that it may serve as a potential target for cancer diagnosis and treatment.

Keywords: AFAP1-AS1; Competing endogenous RNA (ceRNA); Long noncoding RNA (lncRNA); miR-423-5p nasopharyngeal carcinoma (NPC).

MeSH terms

Animals
Cell Proliferation / genetics
Heterografts
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / metabolism*
Nasopharyngeal Carcinoma / genetics*
Nasopharyngeal Carcinoma / metabolism*
Neoplasm Metastasis
RNA, Long Noncoding / genetics*
Signal Transduction
rac GTP-Binding Proteins / metabolism*
rho GTP-Binding Proteins / metabolism*

Substances

AFAP1-AS1 long noncoding RNA, human
MIRN423 microRNA, human
MicroRNAs
RNA, Long Noncoding
rac GTP-Binding Proteins
rho GTP-Binding Proteins