IL-6 stimulates lncRNA ZEB2-AS1 to aggravate the progression of non-small cell lung cancer through activating STAT1.

Abstract:

OBJECTIVE:To illustrate the role of interleukin 6 (IL-6) in the progression of non-small cell lung cancer (NSCLC) via activating STAT1. PATIENTS AND METHODS:The level of IL-6 mRNA in 48 paired NSCLC tissues and matched normal ones was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Kaplan-Meier curves were depicted for assessing the overall survival of NSCLC patients with high or low level of IL-6 mRNA. Subsequently, the ZEB2-AS1 level in A549 cells treated with different doses of IL-6 for different time points was determined. After A549 cells were treated with different doses of IL-6, wound closure assays were performed to assess the migration of cells. Protein levels of pSTAT1 and STAT1 in IL-6-treated A549 cells were detected by Western blot. The regulatory effect of STAT1 on IL-6-induced migration of A549 cells was also evaluated. The interaction between ZEB2-AS1 and STAT1 was explored through Chromatin Immunoprecipitation (ChIP) assay. Finally, the role of ZEB2-AS1/STAT1 axis in regulating NSCLC cells was investigated through rescue experiments. RESULTS:Our results indicated that IL-6 was upregulated in NSCLC tissues and cancer cell lines. NSCLC patients with T3-T4 or accompanied with lymphatic metastasis had a higher IL-6 abundance than those with T1-T2 or without metastatic foci. The worse prognosis was identified in NSCLC patients with high expression of IL-6 compared to those with low expression. ZEB2-AS1 showed dose-dependent and time-dependent increase in IL-6-treated A549 cells. IL-6 treatment gradually enhanced the migration ability of A549 cells in a dose-dependent manner. In IL-6-treated A549 cells, protein level of pSTAT1 was remarkably upregulated, and knockdown of STAT1 significantly reversed the promotive effect of IL-6 on migration ability of A549 cells. The results of ChIP assay verified the interaction between ZEB2-AS1 and STAT1. In addition, ZEB2-AS1 could reverse the regulatory effect of STAT1 on the migration ability of A549 cells. CONCLUSIONS:IL-6 was upregulated in NSCLC and accelerated the progression of NSCLC via activating STAT1/ ZEB2-AS1.

authors

Chen T,Li J,Zhou MH,Xu LJ,Pan TC

doi

10.26355/eurrev_202004_20837

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

3734-3740

issue

7

eissn

1128-3602

issn

2284-0729

journal_volume

24

pub_type

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