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J Exp Clin Cancer Res. 2018 Oct 16;37(1):253. 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.

Lian Y1,2,3, Xiong F1,3, Yang L1,3, Bo H3, Gong Z3, Wang Y3, Wei F1,3, Tang Y2,4, Li X5, Liao Q2,4, Wang H4, Zhou M1,3, Xiang B1,3, Wu X2,6, Li Y2,7, Li X1,3, Chen X1, Li G1,3, Guo C1,3, Zeng Z8,9, Xiong W10,11.

Author information

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)

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