Long noncoding RNA CAR10 promotes lung adenocarcinoma metastasis via miR-203/30/SNAI axis

Xiaolu Ge,Zhezhe Zhang,Yanhong Zhou,Juanjuan Xiang,Ranran Wang,Xiaoling Li,Zhaoyang Zeng,Gui-Yuan Li,Ming Zhou,Liqing Jia,Zheng Li,Lin Jiang

doi:10.1038/s41388-018-0645-x

Abstract

Long noncoding RNAs (lncRNAs) play an important role in lung adenocarcinoma (LUAD) metastasis. Here, we found that lncRNA chromatin-associated RNA 10 (CAR10) was upregulated in the tumor tissue of patients with LUAD and enhanced tumor metastasis in vitro and in vivo. Mechanistically, CAR10 induced epithelial-to-mesenchymal transition (EMT) by directly binding with miR-30 and miR-203 and then regulating the expression of SNAI1 and SNAI2. CAR10 overexpression was positively correlated with a poor prognosis in LUAD patients, whereas overexpression of both CAR10 and SNAI was correlated with even worse clinical outcomes. In conclusion, the CAR10/miR-30/203/SNAI axis is a novel and potential therapeutic target for LUAD.

Highlights

Lung cancer is the most common cause of cancer-related deaths in China and worldwide [1, 2]
chromatin-associated RNA 10 (CAR10) turned out to be upregulated in lung adenocarcinoma (LUAD) cell lines (A549, PC9, and H358) and other tumor cell lines (HepG2 and SW480) compared with human bronchial epithelial cells (HBE) (Fig. 1f)
We found Long noncoding RNAs (lncRNAs) CAR10 to be upregulated in tumor tissues and even more overexpressed in paired metastatic tissues of LUAD

Summary

Introduction

Lung cancer is the most common cause of cancer-related deaths in China and worldwide [1, 2]. Lung adenocarcinoma (LUAD) is the most prominent histological subtype of non-small-cell lung cancer (NSCLC) with a high rate of mortality and metastasis [3]. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a marker for monitoring metastasis progression and predicting survival in non-smallcell lung cancer [8]. MALAT1 increased brain and bone metastasis of LUAD cells [9, 10]. LncRNA ANRIL encoded in chromosomal region 9p21 and in the opposite direction of the INK4B-ARF-INK4A gene cluster is upregulated in NSCLC tissues and is positively associated with metastasis and poor prognosis [11, 12]. ANRIL plays an oncogenic role in LUAD by inhibiting P21 and KLF2 transcription [13]

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