Hypoxia exposure upregulates MALAT-1 and regulates the transcriptional activity of PTB-associated splicing factor in A549 lung adenocarcinoma cells

缺氧暴露上调 A549 肺腺癌细胞中的 MALAT-1 并调节 PTB 相关剪接因子的转录活性

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作者:Ling Hu, Jing Tang, Xiaohuan Huang, Tao Zhang, Xiaoling Feng

Abstract

Hypoxia has been reported to be a critical microenvironmental factor that induces cancer metastasis and proliferation in gastric, liver and hepatic cancers; however, the underlying mechanisms of this are largely unknown. Long noncoding RNAs (lncRNAs) have emerged as crucial factors of several aspects of tumor malignancy, including tumorigenesis, metastasis and chemoresistance. However, the potential association of lncRNAs with hypoxia-induced cancer malignancy remains to be determined. In the present study, the differential expression of lncRNAs following the induction of hypoxia in A549 lung adenocarcinoma cells was analyzed reverse transcription-quantitative polymerase chain reaction. It was identified that the lncRNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) was upregulated significantly by hypoxia in A549 cells. By considering its promotive effects on malignant tumor behaviors, in the present study, it was identified that upregulated MALAT-1 released the binding of PTB-associated splicing factor (PSF) to its target gene, GAGE6, and thus promoted proliferation, migration and invasion of A549 cells following hypoxia exposure. These results advance the overall understanding of the mechanism of hypoxia-induced lung cancer metastasis and may assist in the development of novel therapeutics.

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