lncRNA ELFN1-AS1 promotes proliferation, migration and invasion and suppresses apoptosis in colorectal cancer cells

Sep 24, 2026

Uploaded by Riley

Tumour cells rewire metabolism to sustain high proliferation and resist oxidative stress. lncRNA ELFN1-AS1 is broadly upregulated across cancers and is critical for tumour cell proliferation and apoptosis, yet its metabolic function remained unclear. The study shows that ELFN1-AS1 enhances glucose consumption and drives lactate and NADPH production. Mechanistically, ELFN1-AS1 increases G6PD expression and activates the pentose phosphate pathway via TP53 degradation, while YY1 promotes ELFN1-AS1 transcription. ELFN1-AS1 knockdown suppresses G6PD and tumour growth in mice.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Materials and Methods

Patients and specimens

Original Article lncRNA ELFN1-AS1 promotes proliferation, migration and invasion and suppresses apoptosis in colorectal cancer cells by enhancing G6PD activity Fahong Wu, Wei Zhang, Hangzhi Wei, Hanwei Ma, Guangxian Leng, and Youcheng Zhang* Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou 730030, China *Correspondence address. Tel: +86-13919975286; E-mail: [zhangyouchengphd@163.com](zhangyouchengphd@163.com)[ ](zhangyouchengphd@163.com)Received 22 July 2022 Accepted 23 November 2022 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. Key words lncRNA ELFN1-AS1, colorectal cancer, YY1, TP53, G6PD Introduction Carcinogenesis depends on the reprogramming of tumour cell metabolism as a natural consequence of oncogenic mutations [1] . As first observed by Otto Warburg, tumour cells tend to use large amounts of glucose through aerobic glycolysis [2] . This metabolic change can not only support the energy and macromolecule requirements of tumour cells but also lead to the formation of amicroenvironment conducive to tumour cell growth and survival [3] . Over the past century, key studies on tumour metabolism have identified metabolic reprogramming as a major contributor to tumour progression and have also detected alterations in metabolic reprogramming far exceeding initial expectations [4] . Activation of the pentose phosphate pathway (PPP) is an important consequence of metabolic reprogramming [5] . The PPP is a branch of glycolysis that is catalysed by hexokinase and consumes glucose-6-phosphate as the main substrate. The PPP can produce nicotinamide adenine dinucleotide phosphate (NADPH), which is necessary for the production of reduced glutathione, and glutathione can scavenge reactive oxygen species (ROS) to maintain cell homeostasis. The PPP also generates ribulose-5-phosphate (Ru5P) for nucleotide biosynthesis [6] . Although the PPP plays a key role in tumorigenesis, its specific regulatory mechanism remains unclear. Long noncoding RNAs (lncRNAs) are RNA molecules with transcript lengths of over 200 nt that have no protein-coding potential [7–9] . lncRNAs in the nucleus are mainly involved in epigenetic and transcriptional gene regulation processes, including histone modification, DNA methylation regulation, chromatin remodelling, chromatin modification complex formation, transcription factor activity, and nuclear protein expression [10–15] . Moreover, lncRNAs in the cytoplasm are mainly involved in gene regulation at the posttranscriptional and translational levels; for example, they interact with proteins in the cytoplasm to regulate mRNA metabolism [16–18] . Above results indicate that lncRNAsare extensively involved in the proliferation, migration, invasion and apoptosis of cancer cells. The lncRNA ELFN1-AS1

FAQs

What role does lncRNA ELFN1-AS1 play in colorectal cancer cells?

ELFN1-AS1 promotes proliferation, migration, and invasion, and suppresses apoptosis in colorectal cancer cells.

How does ELFN1-AS1 affect cellular metabolism according to the study?

ELFN1-AS1 enhances glucose consumption and increases lactate and NADPH production by activating the pentose phosphate pathway.

What regulatory axis is validated for ELFN1-AS1 in colorectal cancer?

The study supports a YY1/ELFN1-AS1/TP53/G6PD axis: YY1 binds the ELFN1-AS1 promoter, ELFN1-AS1 promotes TP53 degradation, and this upregulates G6PD and activates PPP.

Sep 24, 2026

Uploaded by Riley