Abstract

BACKGROUND: The aim of this study was to assess the involvement of lncRNA ZEB2-AS1 in the development of NSCLC and to explore the potential mechanism involved.

MATERIAL AND METHODS: ZEB2-AS1 expressions in 48 paired NSCLC tissues and paracancerous tissues were examined by qRT-PCR. ZEB2-AS1 level in NSCLC patients affected by tumor staging and lymphatic metastasis was examined as well. Regulatory effects of ZEB2-AS1 on proliferative, migratory, and invasive properties of NCI-H1650 and HCC827 cells were evaluated. The interaction between ZEB2-AS1 and EZH2 was identified through RIP assay. Subsequently, the binding of EZH2 on PTEN promoter region was tested by ChIP. Finally, rescue experiments were conducted to assess the involvement of PTEN in the development of NSCLC.

RESULTS: ZEB2-AS1 was upregulated in NSCLC tissues and cell lines. Its level was higher in NSCLC patients with T3–T4 or accompanied with lymphatic metastasis relative to those with T1–T2 or without metastatic loci. Knockdown of ZEB2-AS1 suppressed proliferative, migratory, and invasive properties of NCI-H1650 and HCC827 cells. PTEN level was elevated after knockdown of ZEB2-AS1 or EZH2 in HCC827 cells. Subsequently, RIP assay proved the interaction between ZEB2-AS1 and EZH2. Knockdown of ZEB2-AS1 markedly reduced the binding of EZH2 on the PTEN promoter region. Notably, knockdown of PTEN reversed the effects of EZB2-AS1 on regulating proliferative, migratory, and invasive properties of NSCLC cells.

CONCLUSIONS: lncRNA ZEB2-AS1 is upregulated in NSCLC, which elevates the viability and malignant degree of NSCLC cells by downregulating PTEN, thus aggravating the progression of NSCLC.

Keywords: Carcinoma, Non-Small-Cell Lung, PTEN Phosphohydrolase, RNA, Long Noncoding, A549 cells, Cell Movement, Cell Proliferation, China, Disease Progression, Enhancer of Zeste Homolog 2 Protein, Gene Expression Regulation, Neoplastic, Lung Neoplasms, Lymphatic Metastasis, MicroRNAs, Neoplasm Invasiveness, RNA, Antisense, Zinc Finger E-box Binding Homeobox 2