Long intergenic non-protein coding RNA 00858 participates in the occurrence and development of esophageal squamous cell carcinoma through the activation of the FTO-m6A-MYC axis by recruiting ZNF184

Ke, Shun; Wang, Jing; Lu, Jun; Fang, Minghao; Li, Ruichao

doi:10.1016/j.ygeno.2023.110593

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…ZNF184encodes a Kruppel C2H2-type zinc-finger protein family member. ZNF184 is overexpressed in oesophageal squamous cell carcinoma (ESCC) tissues and cells, and the expression of ZNF184 upregulates FTO, thereby enhancing MYC expression and promoting the progression of ESCC[ 29 ]. Moreover, epidemiological studies indicated that ZNF184 was significantly associated with lung cancer ( P = 5.50x10-6)[ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

Li,

Yang,

Wang

et al. 2024

World J Gastrointest Oncol

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BACKGROUND Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo . CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

Li,

Yang,

Wang

et al. 2024

World J Gastrointest Oncol

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“…However, in EC, the mechanism by which m6A modulators regulated c-myc signaling remains largely unknown. Currently, only one relevant study was found showing that LINC00858 upregulates FTO expression by recruiting ZNF184 to inhibit m6A modification of MYC, which promotes proliferation, migration and invasive properties and accelerates apoptosis in EC cells [ 53 ]. And we found that knockdown of SHMT2 could reduce the m6A modification level of c-myc.…”

Section: Discussionmentioning

confidence: 99%

SHMT2 regulates esophageal cancer cell progression and immune Escape by mediating m6A modification of c-myc

Qiao,

Li,

Cheng

et al. 2023

Cell Biosci

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Background In recent years, the role of altered cellular metabolism in tumor progression has attracted widespread attention. Related metabolic enzymes have also been considered as potential cancer therapeutic targets. Serine hydroxymethyltransferase 2 (SHMT2) has been reported to be upregulated in several cancers and associated with poor prognosis. However, there are few studies of SHMT2 in esophageal cancer (EC), and the related functions and mechanisms also need to be further explored. Methods In this study, we first analyzed SHMT2 expression in EC by online database and clinical samples. Then, the biological functions of SHMT2 in EC were investigated by cell and animal experiments. The intracellular m6A methylation modification levels were also evaluated by MeRIP. Linked genes and mechanisms of SHMT2 were analyzed by bioinformatics and rescue experiments. Results We found that SHMT2 expression was abnormally upregulated in EC and associated with poor prognosis. Functionally, SHMT2 silencing suppressed c-myc expression in an m6A-dependent manner, thereby blocking the proliferation, migration, invasion and immune escape abilities of EC cells. Mechanistically, SHMT2 encouraged the accumulation of methyl donor SAM through a one-carbon metabolic network, thereby regulating the m6A modification and stability of c-myc mRNA in a METTL3/FTO/ALKBH5/IGF2BP2-dependent way. In vivo animal experiments also demonstrated that SHMT2 mediated MYC expression by m6A-methylation modification, thus boosting EC tumorigenesis. Conclusion In conclusion, our data illustrated that SHMT2 regulated malignant progression and immune escape of EC cell through c-myc m6A modification. These revealed mechanisms related to SHMT2 in EC and maybe offer promise for the development of new therapeutic approaches.

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“…In ESCC, LINC00858 upregulates FTO expression by recruiting ZNF184. FTO promotes the proliferation, invasion, and migration characteristics of ESCC cells by demethylating MYC and upregulating its expression 81 . Besides indirectly regulating the expression of methylesterases, lncRNAs can also act by recruiting methylesterases to the binding sites of target genes, and lncRNAs can directly catalyze epigenetic modifications of methylesterases to alter their activities.…”

Section: Ncrnas To Methylationmentioning

confidence: 99%

The bidirectional interplay between ncRNAs and methylation modifications in gastrointestinal tumors

Kong,

Yu,

Guo

et al. 2023

Int. J. Biol. Sci.

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The aberrant expression of methylation and ncRNAs, two crucial regulators of epigenetic modifications, has been widely demonstrated in cancer. The complex interplay between them is essential in promoting malignant phenotype, poor prognosis, and drug resistance in GI tumors (including esophageal, gastric, colorectal, liver, and pancreatic cancers). Therefore, we summarize the interrelation process between ncRNAs and methylation modifications in GI tumors, including the detailed mechanism of methylation enzyme regulation of ncRNAs, the molecular mechanism of ncRNAs regulation of methylation modifications, and the correlation between the interactions between ncRNAs and methylation modifications and clinical features of tumors. Finally, we discuss the potential value of ncRNAs and methylation modifications in clinical diagnosis and therapy.

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Long intergenic non-protein coding RNA 00858 participates in the occurrence and development of esophageal squamous cell carcinoma through the activation of the FTO-m6A-MYC axis by recruiting ZNF184

Cited by 4 publications

References 36 publications

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

SHMT2 regulates esophageal cancer cell progression and immune Escape by mediating m6A modification of c-myc

The bidirectional interplay between ncRNAs and methylation modifications in gastrointestinal tumors

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