lncRNA <italic>ELFN1-AS1</italic> promotes proliferation, migration and invasion and suppresses apoptosis in colorectal cancer cells by enhancing <italic>G6PD</italic> activity
Fahong Wu, Wei Zhang, Hangzhi Wei, Hanwei Ma, Guangxian Leng, Youcheng Zhang
Abstract
<p indent="0mm">Tumour cells change their metabolic patterns to support high proliferation rates and cope with oxidative stress. The lncRNA <italic>ELFN1-AS1</italic> is highly expressed in a wide range of cancers and is essential to the proliferation and apoptosis of tumour cells. Nevertheless, its function in the metabolic reprogramming of tumour cells is unclear. Here we show that <italic>ELFN1-AS1</italic> promotes glucose consumption as well as lactate and NADPH production. Database searching, bioinformatics analysis, RNA immunoprecipitation (RIP) and RNA pull-down assays show that <italic>ELFN1-AS1</italic> enhances glucose-6-phosphate dehydrogenase ( <italic>G6PD</italic>) expression and activates the pentose phosphate pathway (PPP) by promoting <italic>TP53</italic> degradation. In addition, luciferase reporter assay and chromatin immunoprecipitation (ChIP) show that <italic>YY1</italic> binds to the <italic>ELFN1-AS1</italic> promoter to promote transcriptional activation of <italic>ELFN1-AS1</italic>. Consistent with the <italic>in vitro</italic> experiments, knockdown of <italic>ELFN1-AS1</italic> impedes the growth of tumours transplanted into mice by inhibiting the expression of <italic>G6PD</italic>. In conclusion, this study reveals that <italic>ELFN1-AS1</italic> activates the PPP, and validates the regulatory role of the <italic>YY1</italic>/ <italic>ELFN1-AS1</italic>/ <italic>TP53</italic>/ <italic>G6PD</italic> axis in colorectal cancer.