<scp>DIAPH3</scp> is a prognostic biomarker and inhibit colorectal cancer progression through maintaining <scp>EGFR</scp> degradation

Huang, Rong‐Yau; Wu, Cheng; Wen, Ji; Yu, Jie; Zhu, Hui; Yu, Jinlong; Zou, Zhaowei

doi:10.1002/cam4.4793

Cited by 7 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, Lin and colleagues [22] reported increased expression of DIAPH1, but not DIAPH3, in colonic carcinoma cells. Recently, a study done by Huang and colleagues [23] concluded that DIAPH3 functions as a tumor suppressor in CRC as DIAPH3 depletion is associated with tumor progression and worse prognosis. Also, DIAPH3 increased expression was seen in prostate and breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence

Foda,

El-Hawary,

Elnaghi

et al. 2024

TUB

View full text Add to dashboard Cite

BACKGROUND: It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the “mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)”, and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types. OBJECTIVE: The aim of the study was to investigate the pattern of immunohistochemical expression of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens. METHODS: The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique. RESULTS: MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P = 0.009) and CRA cases (P = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P = 0.050) and perineural invasion (P = 0.017). CONCLUSIONS: Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence

Foda,

El-Hawary,

Elnaghi

et al. 2024

TUB

View full text Add to dashboard Cite

show abstract

“…DIAPH3 is one of members belong to diaphanous subfamily gene, which engages in actin remodeling and cell movement regulation [6]. Recently, some evidences have indicated a signi cant association between DIAPH3 and tumorigenesis and progression, such as breast cancer, colorectal cancer, and lung cancer [13,19,20]. In this study, we comprehensively explored the correlation of DIAPH3 with expression difference in cancer or normal tissues, prognosis, tumor in ltrating immune cells (TIICs), and immune therapy predictors.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the role of DIAPH3 in Cancers and Validation in Bladder Cancer

Chen

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Cancer is still a serious public health concern across the world at present. Previous studies have suggested that DIAPH3 might play a role in tumorigenesis and progression. However, the prognostic and immunological role of DIAPH3 in human cancers remains unclear. Method The TCGA, GTEx, TIMER2 and GEPIA2 database were utilized to investigate expression difference of DIAPH3 between normal tissues and cancers. For survival analysis, K-M plotter and Pronogscan website were employed. The genetic alteration analysis for DIAPH3 were conducted via cBioPortal database. The DIAPH3 related proteins were screened by the STRING website, and incorporated into KEGG and GO analysis using ‘clusterProfiler' package. Then, we used CIBERSORT algorithm to investigate the percentage of TIICs. For correlation analysis with molecular and immunological subtype, TMB, and MSI, the TISIDB database and SangerBox platform were utilized. To validate the function of DIAPH3 in BLCA, human bladder cancer cells T24 and 5637 were transfection by siRNA and Lipofectamine 8000. The efficiency of knockdown towards target gene was evaluated by qRT-PCR and Western Blot. The CCK-8 assays, clone formation assays, transwell, and wound healing assays were performed to test the proliferation, migration and invasion ability of cells. Results Various type of cancers had increased DIAPH3 expression than normal tissues, and DIAPH3 expression played an adverse prognostic role in most of cancers. Then, function analyses indicated that actin, microtubule and phagocytosis related pathways were enriched in DIAPH3 related proteins. DIAPH3 was strongly correlated to tumor immunity cells infiltration, especially MDSC. In addition, the link between DIAPH3 with immunological subtype, molecular subtype, TMB, and MSI were also observed. Furthermore, the knockdown of DIAPH3 could inhibit the proliferation, migration and invasion of bladder cancer cells. Conclusion In summary, our study demonstrated a correlation between DIAPH3 expression and prognosis, clinicopathological characteristics, immune infiltration cells, and immunotherapy response based on a pan-cancer analysis. The knockdown of DIAPH3 inhibited the proliferation, migration and invasion of bladder cancer cells. These findings might expand our knowledge of DIAPH3 as potential predictive biomarker or therapy target for cancers.

show abstract

“…The more abundant cell type, ACC M, is characterised by the top marker genes DIAPH3 and POLQ that we verified are also overexpressed at the protein levels in ACC. POLQ is a known DNA polymerase [40] and DIAPH3 is a relatively uncharacterised protein that has recently been shown to localise to the centrosome during mitosis [41], and proposed as a biomarker for prostate and colorectal cancer [56,57]. Of note, both POLQ and DIAPH3 are among the top marker genes for transit amplifying cells (TACs) in a recent single-cell data set comparing human colorectal polyps with normal tissue [58], suggesting that ACC M might represent a mitotic phenotype with increased prevalence in the diseased state of many self-renewing tissues such as the colon, intestine and adrenal cortex [59].…”

Section: Discussionmentioning

confidence: 99%

“…and proposed as a biomarker for prostate and colorectal cancer [56,57]. Of note, both POLQ and DIAPH3 are among the top marker genes for transit amplifying cells (TACs) in a recent single-cell data set comparing human colorectal polyps with normal tissue [58], suggesting that ACC M might represent a mitotic phenotype with increased prevalence in the diseased state of many self-renewing tissues such as the colon, intestine and adrenal cortex [59].…”

Section: Tourigny Altieri Et Al 13mentioning

confidence: 99%

Cellular landscape of adrenocortical carcinoma at single-nuclei resolution

Tourigny,

Altieri,

Secener

et al. 2023

Preprint

View full text Add to dashboard Cite

Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with a molecular pathology that remain incompletely understood. To gain novel insights into the cellular landscape of ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC tumour samples and analysed these alongside a previously published snRNA-seq data set from normal adrenal glands (NAGs). We find the ACC tumour microenvironment to be relatively devoid of immune cells compared to NAG tissues, consistent with known high tumour purity values for ACC as an immunologically ``cold'' tumour. Our analysis identifies three separate groups of ACC samples that are characterised by different relative compositions of adrenocortical cell types, including two populations (ACC 1 and ACC 2) that are specifically enriched in the most aggressive tumours and display hallmarks of the epithelial to mesenchymal transition (EMT) and dysregulated steroidogenesis, respectively. In addition to cell types associated with hypoxic and metabolic signatures (ACC 3 and ACC 4) prevalent among less-aggressive tumours, we also identified and validated a population of mitotically active adrenocortical cells (ACC M) strongly overexpressing genes POLQ and DIAPH3 that possibly supports the expansion of malignant cell lineages. The smallest identified ACC specific cell type, ACC 5, displays characteristics of increased proliferation and growth factor signalling, and is therefore a potential progenitor-like or cell-of-origin candidate for the different lineages involved in adrenocortical carcinogenesis. Intriguingly, linage tracing suggests the fate adopted by malignant adrenocortical cells upon differentiation appears to be at least partly associated with the copy number or allelic balance state of the imprinted DLK1/MEG3 genomic locus, which we verified by assessing DNA methylation status among samples from the three groups of tumours defined by their different cell type compositions. Our results therefore provide new insights into the cellular heterogeneity of ACC, indicating that genetic perturbations to a hierarchical cellular differentiation mechanism underlying healthy adrenocortical renewal and zonation may explain the molecular basis for disease pathogenesis.

show abstract

DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation

Cited by 7 publications

References 37 publications

Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence

Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence

Comprehensive Analysis of the role of DIAPH3 in Cancers and Validation in Bladder Cancer

Cellular landscape of adrenocortical carcinoma at single-nuclei resolution

Contact Info

Product

Resources

About