Nicotine promotes the development of non-small cell lung cancer through activating LINC00460 and PI3K/Akt signaling.

Hongying Zhao,Xiubao Ren,Yu Wang

doi:10.1042/bsr20182443

Abstract

Objective: Nicotine, the main ingredient in tobacco, is identified to facilitate tumorigenesis and accelerate metastasis in tumor. Studies in recent years have reported that long intergenic non-protein coding RNA 460 (LINC00460) is strongly associated with lung cancer poor prognosis and nicotine dependence. Nonetheless, it is unclear whether nicotine promotes the development of lung cancer through activation of LINC00460. Methods: We determined that LINC00460 expression in lung cancer tissues and the prognosis in patients with non-small cell lung carcinoma (NSCLC) using Gene Expression Profiling Interactive Analysis (GEPIA) website and The Cancer Genome Atlas (TCGA) database. Through in vitro experiments, we studied the effects of nicotine on LINC00460 in NSCLC cells lines using Cell Counting Kit-8 (CCK-8), transwell test, flow cytometry, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot assays. Results: We identified the significant up-regulated expression level of LINC00460 in NSCLC tissues and cell lines, especially, the negative correlation of LINC00460 expression level with overall survival (OS). In in vitro experiments, LINC00460 was overexpressed in NSCLC cell lines under nicotine stimulation. Nicotine could relieve the effect of LINC00460 knockdown on NSCLC cell proliferation, migration and apoptosis. The same influence was observed on PI3K/Akt signaling pathway. Conclusions: In summary, this is the first time to examine the potential roles of LINC00460 in lung cancer cell proliferation, migration and apoptosis induced by nicotine. This may help to develop novel therapeutic strategies for the prevention and treatment of metastatic tumors from cigarette smoke-caused lung cancer by blocking the nicotine-activated LINC00460 pathway.

Highlights

It is well known that mortality caused by lung cancer ranks first in cancer-related deaths worldwide [1]
We learned from the data of Gene Expression Profiling Interactive Analysis (GEPIA) that LINC00460 was overexpressed in lung adenocarcinoma tissues compared with the normal tissues (Figure 1A, *P
We identified that the effect of LINC00460 knockdown on non-small cell lung cancer (NSCLC) cells’ activities can be restored by administration of nicotine and regulating the PI3K/Akt signaling pathway

Summary

Introduction

It is well known that mortality caused by lung cancer ranks first in cancer-related deaths worldwide [1]. Cigarette smoking comprises almost 90% of all deaths from lung cancer [4,5]. Izzotti et al [6] investigated the expression of 484 microRNAs (miRNAs) in the rat lungs exposed to environmental cigarette smoke for 4 weeks, found that cigarette smoke down-regulates 126 miRNAs at least two-fold and 24 miRNAs more than three-fold. Their dysregulation is associated with the initiation and development of lung cancer, which suggested that tobacco smoke might exert their carcinogenic effects by deregulation of miRNAs [7,8]. Its biosynthesis and regulation in tobacco (Nicotiana tabacum) have been well studied

Methods

Results

Conclusion