Integrated analysis identifies DUSP5 as a novel prognostic indicator for thyroid follicular carcinoma

Zhang, Qian; Xing, Yiqian; Jiang, Shan; Xu, Chunmei; Zhou, Xiaojun; Zhang, Rui; Xie, Tianyue; Zou, Zhiwei; Gong, Piyun; Zhu, Huangao; Zhang, Dongmei; Ma, Huimei; Liao, Lin; Dong, Jianjun

doi:10.1111/1759-7714.13270

Cited by 7 publications

(5 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Downregulation of DUSP5 is associated with poor prognosis in several cancers. 50 , 55 , 56 Here, DUSP5 expression was lower in CADM1 + T cells, which increase during ATL disease progression, 24 , 41 than in CADM1 − T cells, regardless of ATL subtype ( Figure 3 C). Taken together, the results indicate that downregulation of DUSP5 in HTLV-1–infected cells contributes to ATL leukemogenesis and that restoring its expression by combination treatment with DNA demethylating agents and EZH inhibitors has anti-ATL effects.…”

Section: Discussionmentioning

confidence: 91%

Dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth in ATL

et al. 2023

View full text Add to dashboard Cite

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T cells caused by human T-cell lymphotropic virus type 1 (HTLV-1)-induced T-cell transformation. Following infection with HTLV-1, it takes several decades for HTLV-1 carriers to develop ATL. The prognosis of ATL remains poor despite several new agents are approved in the last few years. Recently, it has been noted that epigenetic abnormalities both DNA methylation and tri-methylation at histone H3Lys27 (H3K27me3) contribute to ATL leukemogenesis. Here, we investigated the effect of combination treatment with DNA demethylating agents (azacytidine (AZA), decitabine (DAC), and OR-2100 (OR21), which is silylated derivative of decitabine) and inhibitors of enhancer of zeste homolog 2 (EZH2) (EPZ-6438 and DS-3201b) which catalyze trimethylation of H3K27, in ATL. The combination of DAC and OR21 but not AZA with EZH inhibitors exhibited synergistic anti-ATL effects in vitro and in vivo concomitant with DNA demethylation and reduction of H3K27me3. The combination induced gene expression reprogramming. Dual-specificity phosphatase 5 (DUSP5), an ERK-specific phosphatase, was identified as a key molecule that mediated the inhibitory effect of combination treatment by inactivating the ERK signaling pathway. DUSP5 was downregulated by DNA methylation and H3K27me3 accumulation in the promoter region in HTLV-1-infected cells from ATL patients during ATL leukemogenesis. The present results demonstrate that dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth by restoring DUSP5, and the dual targeting of aberrant DNA and histone methylation is a feasible therapeutic approach for ATL.

show abstract

Section: Discussionmentioning

confidence: 91%

Dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth in ATL

et al. 2023

View full text Add to dashboard Cite

show abstract

“…31 The protein encoded by DUSP5 is a member of the double specific protein phos- PARP inhibitors in the treatment of breast and ovarian cancer. 33 PCR results showed that MYC expression was activated in TPP treated groups. Cell migration related differential genes included PFN1, CKB, MICAL2, SCUBE3, and CXCL8.…”

Section: Discussionmentioning

confidence: 92%

“…However, the exact functions of the gene is not well defined. Recent data has shown that targeting DNPH1 makes BRCA ‐deficient cells sensitive to PARP inhibitors in the treatment of breast and ovarian cancer 33 . PCR results showed that MYC expression was activated in TPP treated groups.…”

Section: Discussionmentioning

confidence: 99%

Low concentration triphenyl phosphate fuels proliferation and migration of hepatocellular carcinoma cells

Zhang

Wang

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

Organophosphate flame retardants (OPFRs) have been widely used due to their unique properties. The OPFRs are mainly metabolized in the liver. However, whether the plasma level of OPFRs was involved in the progression of liver cancer remains unclear. Triphenyl phosphate (TPP) is one of the OPFRs that are mostly detected in environment. In this study, we performed CCK8, ATP, and EdU analyses to evaluate the effect of TPP at the concentrations at 0.025-12.8 μM on the proliferation, invasion, and migration of Hep3B, a hepatocellular carcinoma (HCC) cell line. Tumorbearing mouse model was used for in vivo validation. The results showed that low concentrations of TPP at (0.025-0.1 μM), which are obtained in the plasma of patients with cancers, remarkably promoted cell invasion and migration of Hep3B cells. Animal experiments confirmed that TPP treatment significantly enhanced tumor growth in the xenograft HCC model. To explore the possible molecular mechanisms that might mediate the actions of TPP on Hep3B cells, we profiled gene expression in groups treated with or without TPP at the concentrations of 0.05 and 0.1 μM using transcriptional sequencing. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Protein-protein interaction (PPI) analyses demonstrated that pathways affected by differentially expressed genes (DEGs) were mainly in nuclear-transcribed mRNA catabolic processes, cytosolic ribosome, and ATPase activity. A 0.05 and 0.1 μM TPP led to up-regulation of a series of genes including EREG, DNPH1, SAMD9, DUSP5, PFN1, CKB, MICAL2, SCUBE3, and CXCL8, but suppressed the expression of MCC. These genes have been shown to be associated with proliferation and movement of cells. Taken together, our findings suggest that low concentration of TPP could fuel the proliferation, invasion, and migration of HCC cells. Thus, TPP is a risk factor in the progression of HCC in human beings.Liang Ye and Xu Zhang contributed equally to this work.

show abstract

“…33 Low levels of DUSP5 in FTC are involved in proliferation, migration, and invasion, which further leads to poorer prognosis. Therefore, DUSP5 might serve as a novel therapeutic target for FTC, 34 it remains to be further researchers.…”

Section: Discussionmentioning

confidence: 99%

Prognosis and influencing factors of follicular thyroid cancer

Shen,

Yan,

Chen

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

ObjectivesFollicular thyroid cancer (FTC) is prone to distant metastasis, and patients with distant metastasis often have poor prognosis. In this study, the impact of metastasis and other relevant factors on the prognosis of follicular thyroid carcinoma was examined.MethodsThis was a retrospective study. Data were obtained from Zhejiang Cancer Hospital, Sun Yat‐sen University Cancer Center and Hangzhou First People's Hospital affiliated with Zhejiang University School of Medicine, from January 2009 to June 2021 for 153 FTC patients. The patients were assigned into three groups according to their distant metastasis: distant metastasis at initial diagnosis (M1), distant metastasis during follow‐up (M2), and no evidence of distant metastasis over the course of the study (M0). Data were collected and summarized on clinical data, laboratory parameters, imaging features, postoperative pathologic subtypes, and metastases. The Cox proportional hazard model was used to perform the univariate and multivariate analysis. Kaplan–Meier curves were used to evaluate cancer‐specific survival (CSS).ResultsBased on metastasis, the patients were assigned into three groups, including 31 in the M1 group, 15 in the M2 group, and 107 in the M0 group. These individuals were followed up for an average of 5.9 years, and the group included 46 patients with distant metastasis (31 confirmed at diagnosis and 15 found during follow‐up). Univariate Cox regression analysis showed that age, Hashimoto's thyroiditis (HT), surgery method, postoperative adjuvant therapy, histologic subtype, nodule size, calcification, TSH, and distant metastasis all impacted prognosis. Multivariate Cox regression analysis suggested that histologic subtype (widely invasive; HR: 7.440; 95% CI: 3.083, 17.954; p < 0.001), nodule size (≥40 mm; HR: 8.622; 95% CI: 3.181, 23.369; p < 0.001) and distant metastasis (positive; HR: 6.727; 95% CI: 2.488, 18.186; p < 0.001) were independent risk factors affecting the prognosis of follicular thyroid cancer.ConclusionsHistologic subtype, nodule size, and distant metastasis are important risk factors for the prognosis of follicular thyroid cancer. Patients with metastatic follicular thyroid cancer have a poor prognosis, especially with metastasis at the time of initial diagnosis. As a result, this group of patients requires individualized treatment and closer follow‐up.

show abstract

Integrated analysis identifies DUSP5 as a novel prognostic indicator for thyroid follicular carcinoma

Cited by 7 publications

References 33 publications

Dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth in ATL

Dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth in ATL

Low concentration triphenyl phosphate fuels proliferation and migration of hepatocellular carcinoma cells

Prognosis and influencing factors of follicular thyroid cancer

Contact Info

Product

Resources

About