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

BACKGROUND

Regenerating gene 4 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 in CRC and its association with lipid droplet formation and chemoresistance.

METHODS

We conducted a meta-analysis and bioinformatics and pathological analyses of expression in CRC. The effects of on the phenotypes and related protein expression were also investigated in CRC cells. We detected the impacts of on the chemoresistance and lipid droplet formation in CRC cells. Finally, we analyzed how regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells.

RESULTS

Compared to normal mucosa, mRNA expression was high in CRC ( < 0.05) but protein expression was low. An inverse correlation existed between lymph node and distant metastases, tumor-node-metastasis staging or short overall survival and mRNA overexpression ( < 0.05), but vice versa for protein expression. -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 ( < 0.05). 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 3-kinase-Akt-nuclear factor-κB pathway. was involved in chemoresistance not through de novo lipogenesis, but lipid droplet assembly. inhibited the transcription of acetyl-CoA carboxylase 1 (ACC1) and ATP-citrate lyase (ACLY) by disassociating the complex formation of anti-acetyl (AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY.

CONCLUSION

may be involved in chemoresistance through lipid droplet assembly. reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.