lncRNA <italic>ELFN1-AS1</italic> promotes proliferation, migration and invasion and suppresses apoptosis in colorectal cancer cells by enhancing <italic>G6PD</italic> activity

Abstract

Tumour cells change their metabolic patterns to support high proliferation rates and cope with oxidative stress. The lncRNA ELFN1-AS1 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 ELFN1-AS1 promotes glucose consumption as well as lactate and NADPH production. Database searching, bioinformatics analysis, RNA immunoprecipitation (RIP) and RNA pull-down assays show that ELFN1-AS1 enhances glucose-6-phosphate dehydrogenase ( G6PD ) expression and activates the pentose phosphate pathway (PPP) by promoting TP53 degradation. In addition, luciferase reporter assay and chromatin immunoprecipitation (ChIP) show that YY1 binds to the ELFN1-AS1 promoter to promote transcriptional activation of ELFN1-AS1 . Consistent with the in vitro experiments, knockdown of ELFN1-AS1 impedes the growth of tumours transplanted into mice by inhibiting the expression of G6PD . In conclusion, this study reveals that ELFN1-AS1 activates the PPP, and validates the regulatory role of the YY1 / ELFN1-AS1 / TP53 / G6PD axis in colorectal cancer.

Prostate cancer-associated transcript 6 (PCAT6) promotes epithelial-mesenchymal transition and stemness and worsens prognosis in patients with colorectal cancer

“…LncRNAs are a class of transcripts exceeding 200 nucleotides in length that are characterized by minimal or no protein-coding potential [18][19][20]. LncRNAs were dismissed ″garbage products″ of transcription, but in the past two decades, their involvement in cell proliferation [21,22], apoptosis [23][24][25], metastasis [26,27], and differentiation [28] has been revealed. Furthermore, lncRNAs regulate tumorigenesis and disease progression at both the transcriptional and posttranscriptional levels [29].…”

Role of long non-coding RNA ELFN1-AS1 in carcinogenesis

“…As a result, they enhanced proliferation, invasion, and migration and decreased apoptosis in CRC cell lines. In addition, in vivo experiments revealed that the overexpression of ELFN1-AS1 is associated with a larger tumor xenograft in nude mice.In another study, Fahong Wu et al [ 33 ] demonstrated that ELFN1-AS1 activated the pentose phosphate pathway (PPP) by increasing glucose-6-phosphate dehydrogenase (G6PD) expression. Consequently, ELFN1-AS1 could enhance the malignant characteristics of CRC both in vivo and in vitro by interfering with metabolic pathways.…”

“…Therefore, TP53 could deprive cancer cells of glucose, the primary substrate for PPP [ 60 – 63 ]. Fahong Wu et al [ 33 ] found that ELFN1-AS1 promotes G6PD activity by inducing the degradation of TP53 protein in CRC. The increased G6PD leads to an accumulation of NADPH.…”

The functions and mechanisms of long non-coding RNA in colorectal cancer

“…Further research has revealed the DLGAP1-AS2/CTCF/Myc axis as an oncogenic regulatory pathway in CRC, promoting CRC cell proliferation ( 213 ). Multiple studies have shown that ELFN1-AS1 is highly expressed in CRC and promotes CRC proliferation through various regulatory axes ( 95 , 214 , 215 ). Overexpression of FAM230B promotes tumor growth by increasing the levels of immature miR-1182 in CRC cells, while simultaneously inhibiting the expression levels of mature miR-1182 ( 101 ).…”