LINC02678 as a Novel Prognostic Marker Promotes Aggressive Non-small-cell Lung Cancer.

Dexin Jia,Ying Xing,Weina Fan,Shuai Zhang,Yuechao Liu,Xiaomei Li,Jian Huang,Fanglin Tian,Yimeng Cui,Ruixue Gu,Yaowen Cui,Li Cai,Yuning Zhan,Mengru Cao

doi:10.3389/fcell.2021.686975

Abstract

Non-small-cell lung carcinoma (NSCLC) is considered to be a fatal disease and characterized by a poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to act as biomarkers and therapeutic targets in solid tumors. However, the expression of lncRNAs and their clinical relevance in NSCLC remain undetermined. The gene expression data profiled in The Cancer Genome Atlas and Gene Expression Omnibus (GSE81089) were employed to screen differentially expressed lncRNAs in NSCLC. LINC02678 was found to be upregulated in NSCLC and exhibited hypomethylation of the promoter region in NSCLC tissues. LINC02678 (also called RP11-336A10.5) was associated with poorer overall survival and relapse-free survival in NSCLC patients. In vitro models of gain- and loss-of-function demonstrated that LINC02678 promotes NSCLC progression by promoting NSCLC cell proliferation and cell cycle progression, as well as inducing NSCLC cell migration, invasion and epithelial-mesenchymal transition. LINC02678 was primarily located in the nucleus and could bind with the enhancer of zeste homolog 2 (EZH2). Moreover, we found that LINC02678 knockdown impaired the occupancy capacity of EZH2 and trimethylation of lysine 27 on histone 3 (H3K27me3) at the promoter region of cyclin dependent kinase inhibitor 1B (CDKN1B) and E-cadherin, as confirmed by ChIP-qPCR. A mouse transplantation model further demonstrated that LINC02678 could promote the tumorigenic and metastatic capacities of NSCLC cells. We identified LINC02678 as a tumor promoter in NSCLC, which enhanced the growth and metastasis of NSCLC cells by binding with EZH2, indicating that LINC02678 may serve as a potential biomarker for cancer diagnosis and treatment.

Highlights

Lung cancer is the most common malignancy and the leading cause of cancer-related deaths worldwide
1,346 Long non-coding RNAs (lncRNAs) were upregulated in GSE81089 dataset (Figure 1A and Supplementary Table 1), 3,048 lncRNAs were upregulated in The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD) dataset (Figure 1B and Supplementary Table 2), and 2,710 lncRNAs were upregulated in TCGA-lung squamous cell carcinoma (LUSC) dataset (Figure 1C and Supplementary Table 3), of which 999 lncRNAs were shared among all these three datasets (Figure 1D)
We found that LINC02678 was highly expressed (Figure 2A) and exhibited promoter hypomethylation (Supplementary Figure 1A) in human Non-small-cell lung carcinoma (NSCLC) samples in TCGA datasets

Summary

Introduction

Lung cancer is the most common malignancy and the leading cause of cancer-related deaths worldwide. It causes more than 1.76 million associated deaths, 18.4% of all cancer deaths (Bray et al, 2018). Non-small cell lung cancer (NSCLC) is the main histological type of lung cancer (over 85%). The 5-year survival rate of NSCLC patients is 19% (Siegel et al, 2020). Once the cancer has spread, it is often shown a limited survival (Zheng et al, 2020). It is urgent to seek effective biomarkers for the early diagnosis and individualized treatment of NSCLC

Objectives

Methods

Results

Conclusion