Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly

Q: What is the main goal of the study on REG4 in colorectal cancer?

To clarify the role of REG4 in colorectal cancer and its association with lipid droplet formation and chemoresistance.

Q: How was REG4 investigated in the study?

The study used meta-analysis, bioinformatics, pathological analyses, and CRC cell experiments to assess REG4 expression, cellular phenotypes, signaling, and protein regulation.

Q: What mechanism links REG4 to chemoresistance in CRC cells?

REG4 contributes to chemoresistance through lipid droplet assembly, involving regulation of lipogenic enzymes via effects on transcription and proteasomal degradation rather than de novo lipogenesis.

Sep 24, 2026

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Regenerating gene 4 (REG4) is established as carcinogenic in certain cancers, yet its colorectal cancer (CRC) manifestations and mechanisms remain unclear. This study examines how REG4 relates to lipid droplet formation and chemoresistance in CRC. Using meta-analysis, bioinformatics, and pathological/cell studies, it evaluates REG4 expression, cellular phenotypes, signaling effects, transcriptional regulation, and proteasomal degradation pathways. Findings link REG4 to CRC aggressiveness and chemoresistance via lipid droplet assembly rather than de novo lipogenesis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Abstract

Background

Aim

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Core Tip

| W | J | G | World Journal of
Gastroenterology | | --- | --- | --- | --- | Submit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Gastroenterol 2023 September 21; 29(35): 5104-5124 DOI: 10.3748/wjg.v29.i35.5104 ISSN 1007-9327 (print) ISSN 2219-2840 (online) ORIGINAL ARTICLE Basic Study Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly Cong-Yu Zhang, Rui Zhang, Li Zhang, Zi-Mo Wang, Hong-Zhi Sun, Zheng-Guo Cui, Hua-Chuan Zheng Specialty type: Gastroenterology and hepatology Provenance and peer review: Unsolicited article; Externally peer reviewed. Peer-review model: Single blind Peer-review report’s scientific quality classification Grade A (Excellent): A Grade B (Very good): B Grade C (Good): 0 Grade D (Fair): 0 Grade E (Poor): 0 P-Reviewer: Batyrbekov K, Kazakhstan; Osera S, Japan Received: June 25, 2023 Peer-review started: June 25, 2023 First decision: August 8, 2023 Revised: August 10, 2023 Accepted: August 25, 2023 Article in press: August 25, 2023 Published online: September 21, 2023 Cong-Yu Zhang, Zi-Mo Wang, Hong-Zhi Sun, Hua-Chuan Zheng, Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China Rui Zhang, Department of Colorectal Surgery, Liaoning Cancer Hospital, Shenyang 110042, Liaoning Province, China Li Zhang, Department of Oncology, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China Zheng-Guo Cui, Department of Environmental Health, University of Fukui School of Medical Sciences, Fukui 910-1193, Japan Corresponding author: Hua-Chuan Zheng, MD, PhD, Professor, Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, No. 2 Fifth Duan, Renmin Street, Guta District, Jinzhou 121001, Liaoning Province, [China.](China. zheng_huachuan@hotmail.com)[ zheng_huachuan@hotmail.com](China. zheng_huachuan@hotmail.com) Abstract BACKGROUND Regenerating gene 4 (REG4) has been proved to be carcinogenic in some cancers, but its manifestation and possible carcinogenic mechanisms in colorectal cancer (CRC) have not yet been elucidated. Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism. AIM To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance. METHODS We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC. The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells. We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells. Finally, we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells. RESULTS Compared to normal mucosa, REG4 mRNA expression was high in CRC (P < 0.05) but protein expression was low. An inverse correlation existed between lymph WJG [https://www.wjgnet.com](https://www.wjgnet.com) 5104 September 21, 2023 Volume 29 Issue 35 Zhang CY et al. REG4 and CRC node and distant metastases, tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression (P < 0.05), but vice versa for REG4 protein expression. REG4-related genes included: Chemokine activity; taste receptors; protein-DNA and DNA packing complexes; nucleosomes and chromatin; generation of second messenger molecules; programmed cell death signals; epigenetic regulation and DNA methylation; transcription repression and activation by DNA binding; insulin signaling pathway; sugar metabolism and transfer; and neurotransmitter receptors (P < 0.05) . REG4 exposure or overexpression promoted proliferation, antiapoptosis, migration, and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide

FAQs

What is the main goal of the study on REG4 in colorectal cancer?

To clarify the role of REG4 in colorectal cancer and its association with lipid droplet formation and chemoresistance.

How was REG4 investigated in the study?

The study used meta-analysis, bioinformatics, pathological analyses, and CRC cell experiments to assess REG4 expression, cellular phenotypes, signaling, and protein regulation.

What mechanism links REG4 to chemoresistance in CRC cells?

REG4 contributes to chemoresistance through lipid droplet assembly, involving regulation of lipogenic enzymes via effects on transcription and proteasomal degradation rather than de novo lipogenesis.

Sep 24, 2026

Uploaded by Cart