ZC3HAV1 promotes the proliferation and metastasis via regulating KRAS in pancreatic cancer

Huang, Wei; Hua, Hao; Xiao, Guoliang; Yang, Xianjin; Yang, Qin; Jin, Lü

doi:10.18632/aging.203296

Cited by 11 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EPRS was reported as a critical regulator of cell proliferation and estrogen signaling in ER + breast cancer [ 109 ] and has also been implicated as a potential treatment target for basal-like breast cancer [ 92 ]. ZC3HAV1, a PARP family enzyme, promotes proliferation and metastasis by regulating KRAS in pancreatic cancer [ 110 ] and is involved in facilitating DNA repair and promoting tumorigenesis in breast cancer [ 93 ].…”

Section: Discussionmentioning

confidence: 99%

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection

Raj-Kumar,

Lin,

Liu

et al. 2024

Breast Cancer Res

View full text Add to dashboard Cite

Background Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors. Methods We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers. Results We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA–protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors. Conclusions This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection

Raj-Kumar,

Lin,

Liu

et al. 2024

Breast Cancer Res

View full text Add to dashboard Cite

show abstract

“…As a member of the MAPK family, ERK1/2 transduces extracellular signals to intracellular signaling cascades, thereby regulating cell behaviors, including cell proliferation and differentiation [ 48 ]. Numerous studies have shown that the ERK/MAPK signaling pathway has crucial roles in tumorigenesis and metastasis [ 49 , 50 ]. HOXC6 has been shown to facilitate the proliferation and migration of glioblastoma cells by activating the ERK/MAPK signaling pathway [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development

Wang

Zhong

et al. 2022

Burns &Amp; Trauma

View full text Add to dashboard Cite

Background A keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However, the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts, providing new ideas for the prevention and treatment of keloids. Methods We utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 (HOXC6) emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction, western blot (WB) and immunohistochemistry. Subsequently, the effects of downregulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8, flow cytometry, transwell migration and WB assays. Meanwhile, we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments. Results HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of HOXC6 inhibited proliferation, migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with HOXC6 in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of HOXC6 in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates HOXC6, contributing to KFs proliferation, migration, apoptosis inhibition and collagen accumulation through the ERK signaling pathway. Conclusions Our findings first revealed that HOXC6 acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation, migration and ECM production by KFs, contributing to the progression of keloids. Taken together, HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.

show abstract

“…ZC3HAV1 (zinc finger CCCH-type antiviral protein 1), also known as PPAR13 [poly (ADP-ribose) polymerase-13] and ZAP (zinc-finger antiviral protein), is a PARP family member of RNA-binding proteins and has important functions in the cellular response to stress [ 41 ]. Studies have shown that it increases cell sensitivity to apoptosis [ 42 ], participates in facilitating DNA repair and promoting tumorigenesis of breast cancer [ 43 ], and facilitates metastasis and proliferation in pancreatic cancer [ 44 ], suggesting that it can be involved in malignant transformation and the development of cancer.…”

Section: Discussionmentioning

confidence: 99%

Construction of a breast cancer prognosis model based on alternative splicing and immune infiltration

et al. 2022

View full text Add to dashboard Cite

Background Breast cancer (BC) is the most common malignancy among women in the world. Alternative splicing (AS) is an important mechanism for regulating gene expression and producing proteome diversity, which is closely related to tumorigenesis. Understanding the role of AS in BC may be helpful to reveal new therapeutic targets for clinical interventions. Methods RNA-seq, clinical and AS data of TCGA-BRCA were downloaded from TCGA and TCGA SpliceSeq databases. AS events associated with prognosis were filtered by univariate Cox regression. The AS risk model of BC was built by Lasso regression, random forest and multivariate Cox regression. The accuracy of the AS risk model and clinicopathological factors were evaluated by time-dependent receiver operating characteristic (ROC) curves. The significant factors were used to construct the nomogram model. Tumor microenvironment analysis, immune infiltration and immune checkpoint analysis were performed to show the differences between the high and low AS risk groups. The expression differences of genes of AS events constituting the risk model in tumor tissues and normal tissues were analyzed, the genes with significant differences were screened, and their relationship with prognosis, tumor microenvironment, immune infiltration and immune checkpoint were analyzed. Finally, Pearson correlation analysis was used to calculate the correlation coefficient between splicing factors (SF) and prognostic AS events in TCGA-BRCA. The results were imported into Cytoscape, and the associated network was constructed. Results A total of 21,232 genes had 45,421 AS events occurring in TCGA-BRCA, while 1604 AS events were found to be significantly correlated with survival. The BRCA risk model consisted of 5 AS events, (TTC39C|44853|AT*− 2.67) + (HSPBP1|52052|AP*− 4.28) + (MAZ|35942|ES*2.34) + (ANK3|11845|AP*1.18) + (ZC3HAV1|81940|AT*1.59), which were confirmed to be valuable for predicting BRCA prognosis to a certain degree, including ROC curve, survival analysis, tumor microenvironment analysis, immune infiltration and immune checkpoint analysis. Based on this, we constructed a nomogram prediction model composed of clinicopathological features and the AS risk signature. Furthermore, we found that MAZ was a core gene indicating the connection of tumor prognosis and AS events. Ultimately, a network of SF-AS regulation was established to reveal the relationship between them. Conclusions We constructed a nomogram model combined with clinicopathological features and AS risk score to predict the prognosis of BC. The detailed analysis of tumor microenvironment and immune infiltration in the AS risk model may further reveal the potential mechanisms of BC recurrence and development.

show abstract

ZC3HAV1 promotes the proliferation and metastasis via regulating KRAS in pancreatic cancer

Cited by 11 publications

References 28 publications

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection

Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development

Construction of a breast cancer prognosis model based on alternative splicing and immune infiltration

Contact Info

Product

Resources

About