The m <sup>6</sup>A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN

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Abstract

Background

Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear.

Methods

The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT–PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1.

Results

The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m ⁶A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells.

Conclusions

Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12943-024-01962-8.

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Author and article information

Contributors

Jun Song:

ORCID: http://orcid.org/0000-0002-6350-2695

songjun@xzhmu.edu.cn

Journal

Journal ID (nlm-ta): Mol Cancer

Journal ID (iso-abbrev): Mol Cancer

Title: Molecular Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-4598

Publication date (Electronic): 16 March 2024

Publication date PMC-release: 16 March 2024

Publication date Collection: 2024

Volume: 23

Electronic Location Identifier: 55

Affiliations

[1 ]GRID grid.413389.4, ISNI 0000 0004 1758 1622, Department of General Surgery, , The Affiliated Hospital of Xuzhou Medical University, ; Xuzhou, Jiangsu 221006 China

[2 ]Institute of Digestive Diseases, Xuzhou Medical University, ( https://ror.org/035y7a716) Xuzhou, Jiangsu 221002 China

[3 ]Affiliated First Clinical College, Xuzhou Medical University, ( https://ror.org/035y7a716) Xuzhou, Jiangsu 221004 China

[4 ]GRID grid.413389.4, ISNI 0000 0004 1758 1622, Central Laboratory, , The Affiliated Hospital of Xuzhou Medical University, ; Xuzhou, Jiangsu 221002 China

[5 ]GRID grid.417303.2, ISNI 0000 0000 9927 0537, Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, , Xuzhou Medical University, ; Xuzhou, Jiangsu 221004 China

[6 ]Department of Radiation Oncology, The Affiliated Hospital of Jiangsu University, ( https://ror.org/028pgd321) Zhenjiang, Jiangsu 212001 China

Author information

Jun Song http://orcid.org/0000-0002-6350-2695

Article

Publisher ID: 1962

DOI: 10.1186/s12943-024-01962-8

PMC ID: 10943897

PubMed ID: 38491348

SO-VID: 34073522-5472-4101-8cff-3349c498c3af

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 14 December 2023

Date accepted : 19 February 2024

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 82203486

Award ID: 82073133

Funded by: FundRef http://dx.doi.org/10.13039/501100004608, Natural Science Foundation of Jiangsu Province;

Award ID: BK20231159

Funded by: Scientific Research of Jiangsu Health Committee

Award ID: ZDA2020005

Funded by: Six Talents Peak’ High-level Talent Project of Jiangsu Province

Award ID: WSW-050

Funded by: Xuzhou Medical Leading Talents Training Project

Award ID: XWRCHT20210034

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: colorectal cancer,pou6f2-as1,fatty acid metabolism,growth

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: colorectal cancer, pou6f2-as1, fatty acid metabolism, growth