Recent evidence has proven that long noncoding RNAs (lncRNAs) play important roles in cancer biology, while few lncRNAs have been characterized in NSCLC. Here, we characterized a novel lncRNA, SBF2 antisense RNA 1 (SBF2-AS1), in non-small cell lung cancer (NSCLC).
Researchers at Nanjing Medical University used quantitative real-time PCR to quantify SBF2-AS1 expression in NSCLC tissues and cell lines. The correlation of SBF2-AS1 expression with clinicopathologic features was analyzed in a cohort NSCLC patient. Loss of function and gain of function studies were performed to determine the effects of SBF2-AS1 on proliferation and metastasis of NSCLC cells. RNA immunoprecipitation and chromosome immunoprecipitation assay was performed to confirm the interaction between SBF2-AS1 with protein and chromosome.
The researchers confirmed that SBF2-AS1 was significantly upregulated in NSCLC compared with corresponding non-tumor tissues, and a high expression level of SBF2-AS1 was correlated with lymph node metastasis and advanced TNM stage. Using siRNAs specifically targeting SBF2-AS1 and plasmid vector, they successfully silenced and overexpressed SBF2-AS1 in NSCCLC cell lines and investigated its biological function both in vitro and in vivo. After the silencing of SBF2-AS1, the metastasis of NSCLC cells was significantly inhibited, the silencing of SBF2-AS1 decreased the proliferation of NSCLC cells, and the cell cycle was arrested at the G1 phase; while overexpression promoted proliferation ability. Xenograft tumor models revealed that the silencing of SBF2-AS1 inhibited tumor growth in vivo. The researchers speculated that SBF2-AS1 might negatively regulate P21. RNA immunoprecipitation discovered that SBF2-AS2 could bind with a core component of polycomb repressive complex2, SUZ12. Additionally chromatin immunoprecipitation assay demonstrated that, after silencing SBF2-AS1, the enrichment of SUZ12 and trimethylation of histone 3 lysine 27 decreased at the promoter region of P21.
Xenograft tumor models were developed in nude mice by A549 cells
transfected with NC and siRNA targeting SBF2-AS1.
The xenograft tumor volume (a, b, c) and weight (d) in the SBF2-AS1 siRNA group were significantly lower than those in the NC group. Immunohistochemistry assay showed that Ki-67 staining was weaker in the siRNA group (e)
SBF2-AS1 may serve as a novel biomarker and potential therapeutic target for NSCLC patients.