Long noncoding antisense RNA FAM83A-AS1 promotes lung cancer cell progression by increasing FAM83A

Abstract

The abnormal expression of long noncoding RNAs (lncRNAs) is closely associated with human cancers. As one special group of lncRNAs, natural antisense transcripts (NATs) can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Their expression levels are altered in many cancers, but their roles are poorly understood. We strove to find NATs involved in human non-small-cell lung cancer (NSCLC) and to reveal their mechanism of action in cancer. We analysed the NATs in NSCLC from the TCGA database by circlncRNAnet. One NAT, family with sequence similarity 83 member A antisense RNA 1 (FAM83A-AS1), was found to be markedly upregulated and positively correlated with its cognate sense counterpart, FAM83A, in NSCLC. Moreover, overexpression of FAM83A-AS1 increased FAM38A protein levels and induced ERK1/2 phosphorylation downstream of FAM83A in cells. Finally, overexpression of FAM83A-AS1 promoted LUAD cell proliferation and invasion. In summary, lncRNA FAM83A-AS1 promotes LUAD by increasing FAM83A expression.

Keywords: FAM83A; FAM83A-AS1; long noncoding RNA; natural antisense transcripts; non-small-cell lung cancer.

Figure 1

Principal component analysis showed that the tumour and normal samples were distinctly clustered by their lncRNA expression levels in LUAD (A), and LUSC (B). lncRNA, long noncoding RNA; LUAD; lung adenocarcinoma; LUSC, lung squamous cell carcinoma

Figure 2

The upregulated NATs in LUAD and LUSC. (A) The upregulated NATs in LUAD and LUSC from the circlncRNAnet database. (B) The expression levels of FOXD3‐AS1, FAM83A‐AS1, FEZF1‐AS1, BARX1‐AS1, NOVA1‐AS1, POU6F2‐AS2, NPSR1‐AS1, BBOX 1‐AS1, KCNMB2‐AS1, and ZFPM2‐AS1 in five LUAD tissues and five LUSC tissues by qRT‐PCR. *P < 0.05; **P < 0.01; ***P < 0.001. LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; NAT, natural antisense transcript; qRT‐PCR, quantitative real‐time PCR

Figure 3

The correlation between FAM83A‐AS1 and FAM83A mRNA in LUAD and LUSC. (A,B) The correlation between FAM83A‐AS1 and FAM83A mRNA in LUAD (A), and LUSC (B) from the TCGA data. (C) The correlation between FAM83A‐AS1 and FAM83A mRNA in five LUAD tissues and five LUSC tissues as identified by qRT‐PCR. (D,E) The expression levels of FAM83A mRNA in normal and cancer tissues from LUAD (D) or LUSC (E) patients in the TCGA data. (F) The expression levels of FAM83A mRNA in paired normal and cancer tissues from five patients with LUAD and five with LUSC as revealed by qRT‐PCR. *P < 0.05; **P < 0.01; ***P < 0.001. LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; mRNA; messenger RNA; qRT‐PCR, quantitative real‐time PCR; TGCA, The Cancer Genome Atlas

Figure 4

The function of FAM83A‐AS1 in lung cancer. (A,B) The relative levels of FAM83A‐AS1 (A) and FAM83A mRNA (B) in A549 cells transfected with an empty vector or the FAM83A‐AS1 overexpression vector. (C) Protein expression in A549 cells transfected with an empty vector or the FAM83A‐AS1 overexpression vector. (D) Growth curves of A549 cells transfected with an empty vector or the FAM83A‐AS1 overexpression vector. (E,F) Transwell assays of A549 cells transfected with an empty vector or the FAM83A‐AS1 overexpression vector. *P < 0.05; **P < 0.01; ***P < 0.001. mRNA, messenger RNA