Long non-coding RNA LUCAT1 is associated with poor prognosis in human non-small lung cancer and regulates cell proliferation via epigenetically repressing p21 and p57 expression.

Yue Sun,Shi-Dai Jin,Liang Han,Wei Wang,Ren-Hua Guo,Feng Wang,Xi-Yi Lu,Quan Zhu,Jing Feng

doi:10.18632/oncotarget.16044

Abstract

Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor–node–metastasis (TNM) stage and overall survival (OS). Further experiments showed that LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo. Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest. We further demonstrated that LUCAT1 was associated with polycomb repressor complexes (PRC2) and that this association was required for epigenetically repression of p21 and p57, thus contributing to the regulation of NSCLC cell cycle and proliferation. In summary, our results show that LUCAT1 could regulate tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.

Highlights

Lung cancer is the main cause of cancer death world-wide, and non-small-cell lung cancer (NSCLC) accounts for nearly 85% of those cases [1]
We discovered that long non-coding RNAs (lncRNAs) lung cancer associated transcript 1 (LUCAT1) was significantly increased in NSCLC tissues compared with the adjacent non-cancerous tissues
The results revealed that the level of LUCAT1 increased significantly in the corresponding adjacent non-normal tissues; as shown in Figure 2A, the LUCAT1 level in NSCLC tissues were nearly 3.79-fold enhanced compared with normal controls

Summary

Introduction

Lung cancer is the main cause of cancer death world-wide, and NSCLC accounts for nearly 85% of those cases [1]. Clinical and experimental oncology have been exceptional progress in recent years, the prognosis for the majority of lung cancer cases remains poor, as the 5-year overall survival rate is approximately 15% [2, 3]. There is an urgent need to provide detailed knowledge of the molecular mechanisms underlying NSCLC progression, which is crucial for improving the prevention, diagnosis, treatment, and survival rate of NSCLC. The dysregulation of lncRNAs has a functional role in diverse cancers, such as lung cancer, gastric cancer, and breast cancer [9,10,11]. Www.impactjournals.com/oncotarget researchers have reported that lncRNAs could serve as biomarkers for the diagnosis of a variety of diseases [12, 13]. It is important to identify cancerassociated lncRNAs and investigate their molecular and biological roles in tumors

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Conclusion