DERL3 suppresses colorectal cancer metastasis through negatively regulating MYCN level

Yu, Fang; Mou, Bo; Shi, Juan; Liu, Jinghua; Qin, Xiang-Xin; Yu, Jia-Man

doi:10.23736/s0026-4806.20.06657-4

Cited by 9 publications

(8 citation statements)

References 20 publications

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“…Studies have shown that MYCN directly regulates the expression of several ABC transporter proteins by binding to their promoter regions ( 22 , 23 ). In recent years, MYCN's function in various tumors, including CRC, has been increasingly explored ( 36 ). MYCN expression and degradation are regulated by various modifications, such as methylation and phosphorylation, at sites such as S62 and T58 in the conserved sequence of MYC Box I ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

RPF2 mediates the CARM1‑MYCN axis to promote chemotherapy resistance in colorectal cancer cells

Lu,

Hu,

Cheng

et al. 2023

Oncol Rep

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Ribosome production factor 2 homolog (RPF2) plays an important role in the life processes of ribosomal biogenesis; however, the function and mechanism of RPF2 in tumors are unclear. The present study demonstrated that RPF2 expression is involved in chemoresistance in colorectal cancer (CRC) cells. The current study demonstrated that upregulation of RPF2 expression in CRC promoted resistance to chemotherapeutic agents in CRC cells, whereas knockdown of RPF2 leads to increased sensitivity of CRC to chemotherapy. In addition, it was found that overexpression of RPF2 led to an increase in ATP-binding cassette (ABC)B1 expression in CRC cells; accordingly, inhibition of RPF2 reduced the level of ABCB1 in CRC cells, thus suggesting that ABCB1 may be a downstream factor of RPF2 in the promotion of chemotherapy resistance to CRC. The results also suggested that the expression of N-myc proto-oncogene protein (MYCN), an upstream regulator of ABCB1, was affected by RPF2 in CRC cells. In addition, it was also found that the downstream protein coactivator-associated arginine methyltransferase 1 (CARM1) of RPF2 existed in direct binding to MYCN and this interaction was regulated by RPF2. The above results suggested that RPF2 is probably regulated ABCB1 expression in CRC through the CARM1-MYCN pathway, thereby promoting CRC drug resistance.

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Section: Discussionmentioning

confidence: 99%

RPF2 mediates the CARM1‑MYCN axis to promote chemotherapy resistance in colorectal cancer cells

Lu,

Hu,

Cheng

et al. 2023

Oncol Rep

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“…Additionally, LINC00702 is upregulated in ovarian cancer cells and promotes ovarian tumor development by interacting with EZH2 and inhibiting KLF2 [ 16 ]. In contrast, LINC00702 is expressed at low levels and suppresses the proliferation of non-small-cell lung and colorectal cancers by controlling the PTEN axis [ 27 , 28 ]. Moreover, LINC00702 mediates DUSP1 transcription to prevent bladder cancer progression [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of LINC00702 inhibits the growth and induces apoptosis of breast cancer through the Wnt/β-catenin pathway

Chai,

Yang,

Liu

et al. 2023

Heliyon

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“…During the UPR, DERL3 is upregulated by ATF6 and enhances the degradation of misfolded proteins ( 48 ). Several studies reported the role of DERL3 as a tumor suppressor in colorectal ( 49 ), gastric ( 50 ), and lung cancers ( 51 ). SERPINH1 (serpin peptidase inhibitor, clade H, member 1) is a kind of serine proteinase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a prognosis prediction model based on 18 endoplasmic reticulum stress-related genes for patients with lung adenocarcinoma

2022

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BackgroundEndoplasmic reticulum (ER) stress had a crucial impact on cell survival, proliferation, and metastasis in various cancers. However, the role of ER stress in lung adenocarcinoma remains unclear.MethodGene expression and clinical data of lung adenocarcinoma (LUAD) samples were extracted from The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. ER stress score (ERSS) was constructed based on hub genes selected from 799 ER stress-related genes by least absolute shrinkage and selection operator (LASSO) regression. A Cox regression model, integrating ERSS and the TNM stage, was developed to predict overall survival (OS) in TCGA cohort and was validated in GEO cohorts. Gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), and gene mutation analyses were performed to further understand the molecular features of ERSS. The tumor immune infiltration was evaluated by ESTIMATE, CIBERSORT, and xCell algorithms. The receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the risk model. p< 0.05 was considered statistically significant.ResultsOne hundred fifty-seven differentially expressed genes (DEGs) were identified between tumor and para-carcinoma tissues, and 45 of them significantly correlated with OS. Next, we identified 18 hub genes and constructed ERSS by LASSO regression. Multivariate analysis demonstrated that higher ERSS (p< 0.0001, hazard ratio (HR) = 3.8, 95%CI: 2.8–5.2) and TNM stage (p< 0.0001, HR = 1.55, 95%CI: 1.34–1.8) were independent predictors for worse OS. The prediction model integrating ERSS and TNM stage performed well in TCGA cohort (area under the curve (AUC) at five years = 0.748) and three GEO cohorts (AUC at 5 years = 0.658, 0.717, and 0.739). Pathway enrichment analysis showed that ERSS significantly correlated with unfolded protein response. Meanwhile, pathways associated with the cell cycle, growth, and metabolism were significantly enriched in the high ERSS group. Patients with SMARCA4, TP53, and EGFR mutations showed significantly higher ERSS (p = 4e−04, 0.0027, and 0.035, respectively). Tissues with high ERSS exhibited significantly higher infiltration of M1 macrophages, activated dendritic cells, and lower infiltration of CD8+ T cells and B cells, which indicate an activated tumor antigen-presenting but suppressive immune response status.ConclusionWe developed and validated an ER stress-related risk model that exhibited great predictive value for OS in patients with LUAD. Our work also expanded the understanding of the role of ER stress in LUAD.

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DERL3 suppresses colorectal cancer metastasis through negatively regulating MYCN level

Cited by 9 publications

References 20 publications

RPF2 mediates the CARM1‑MYCN axis to promote chemotherapy resistance in colorectal cancer cells

RPF2 mediates the CARM1‑MYCN axis to promote chemotherapy resistance in colorectal cancer cells

Knockdown of LINC00702 inhibits the growth and induces apoptosis of breast cancer through the Wnt/β-catenin pathway

Development and validation of a prognosis prediction model based on 18 endoplasmic reticulum stress-related genes for patients with lung adenocarcinoma

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