"SIRT8" expressed in thyroid cancer is actually SIRT7.
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ABSTRACT:
SUBMITTER: Frye R
PROVIDER: S-EPMC2376300 | biostudies-literature | 2002 Dec
REPOSITORIES: biostudies-literature
Publications
"SIRT8" expressed in thyroid cancer is actually SIRT7.
British journal of cancer 20021201 12
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Project description:BackgroundPapillary thyroid cancer (PTC) is one of the malignant tumors with rapidly increasing morbidity and mortality. Sirtuin 7 (SIRT7) is a desuccinylase that is involved in tumorigenesis. The activation of large tumor suppressor 1 (LATS1) can effectively suppress tumorigenesis in multiple tumors and can be affected by SIRT7. This study aimed to explore the role and mechanism of SIRT7 in PTC progression.MethodsThe RNA and protein levels were detected by quantitative real-time PCR (qPCR) and western blot, respectively. Cell proliferation was measured by cell counting kit-8 and colony formation. The apoptosis of PTC cells was analyzed by flow cytometry and Live/dead cell staining. The interaction between proteins was detected by co-immunoprecipitation.ResultsThe results showed that SIRT7 was highly expressed in PTC tissues and cells. Functional studies showed that knockdown of SIRT7 inhibited the proliferation and induced apoptosis of PTC cells. Mechanistically, SIRT7 could directly interact with LATS1 and reduce the stability of the LATS1 protein. Later, rescue experiments suggested that LATS1 silencing reversed the effect of SIRT7 knockdown on PTC cell growth and apoptosis. In addition, SIRT7 promoted tumor growth in vivo.ConclusionTaken together, silencing of SIRT7 promotes the succinylation of LATS1 to enhance LATS1 stability, thus inhibiting the progression of PTC. Therefore, SIRT7 and LATS1 may become novel and potential therapeutic targets for PTC.
| S-EPMC11887367 | biostudies-literature
Project description:ObjectiveThis study was designed to investigate the regulatory effects of kinesin family member (KIF) 23 on anaplastic thyroid cancer (ATC) cell viability and migration and the underlying mechanism.MethodsReverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the levels of KIF23 in ATC cells. Besides, the effects of KIF23 and sirtuin (SIRT) 7 on the viability and migration of ATC cells were detected using cell counting kit-8, transwell and wound healing assays. The interaction between SIRT7 and KIF23 was evaluated by co-immunoprecipitation (Co-IP) assay. The succinylation (succ) of KIF23 was analyzed by western blot.ResultsThe KIF23 expression was upregulated in ATC cells. Silencing of KIF23 suppressed the viability and migration of 8505C and BCPAP cells. The KIF23-succ level was decreased in ATC cells. SIRT7 interacted with KIF23 to inhibit the succinylation of KIF23 at K537 site in human embryonic kidney (HEK)-293T cells. Overexpression of SIRT7 enhanced the protein stability of KIF23 in HEK-293T cells. Besides, overexpression of KIF23 promoted the viability and migration of 8505C and BCPAP cells, which was partly blocked by silenced SIRT7.ConclusionsSIRT7 promoted the proliferation and migration of ATC cells by regulating the desuccinylation of KIF23.
| S-EPMC10870498 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and its dismal prognosis indicates the urgent need to elucidate the potential oncogenic mechanisms. SIRT7 is a classic NAD+-dependent deacetylase that stabilizes the transformed state of cancer cells. However, its functional roles in PDAC are still unclear. Here, we found that SIRT7 expression is upregulated and predicts poor prognosis in PDAC. Then we screened the new interacting proteins of SIRT7 by mass spectrometry and the results showed that SIRT7 can interact with O-GlcNAc transferase (OGT). O-GlcNAcylation stabilizes the SIRT7 protein by inhibiting its interaction with REGγ to prevent degradation, and hyper-O-GlcNAcylation in pancreatic cancer cells leads to hypoacetylation of H3K18 via SIRT7, which promotes transcriptional repression of several tumour suppressor genes. In addition, SIRT7 O-GlcNAcylation at the serine 136 residue (S136) is required to maintain its protein stability and deacetylation ability. In vivo and in vitro experiments showed that blocking SIRT7 O-GlcNAcylation at S136 attenuates tumour progression. Collectively, we demonstrate that O-GlcNAcylation is an important post-translational modification of SIRT7 in pancreatic cancer cells, and elucidating this mechanism of SIRT7 is expected to pave the way for the development of novel therapeutic methods in the future.
| S-EPMC9525610 | biostudies-literature
Project description:Thyroid cancer is the most common endocrine cancer with predominant prevalence of papillary thyroid cancer (PTC) histotype. MAPK signaling genetic alterations are frequent in PTC, affecting more than 80% of cases. These alterations constitutively activate MAPK signaling cross-regulating different pro-oncogenic pathways. However, additional molecular alterations associated with thyroid cancer are not completely understood. In this extent, the new family of proteins named FAM83 (FAMily with sequence similarity 83) was recently identified as mediator of oncogenic signaling in different types of cancer. Here we report FAM83F as a novel highly expressed protein in PTC. We evaluated FAM83F levels in 106 PTC specimens, 34 goiter, and 41 adjacent non-tumoral human thyroid, and observed FAM83F cytoplasmic overexpression in 71% of PTC (76 of 106) while goiter tissues showed nuclear positivity and normal thyroid showed no staining by immunohistochemistry. Moreover, TSH-induced goiter and BRAF T1799A -induced PTC animal models also showed FAM83F activation. In vitro, we generated a stable thyroid cell line PCCL3 with FAM83F overexpression and observed that FAM83F deregulates thyroid follicular cell biology leading to loss of thyroid differentiation genes such as Sodium-Iodide Symporter (NIS), reactivation of stem cell markers such as LIN28B and SOX2, induction of cell migration and resistance to doxorubicin-induced apoptosis. Moreover, FAM83F activates MAPK signaling through interaction with BRAF and RAF while impairs TGFβ antiproliferative signaling transduction. In this study, we showed FAM83F as a new pro-oncogenic protein overexpressed in thyroid cancer that modulates thyroid follicular cell biology and differentiation through cross-regulation of MAPK and TGFβ signaling.
| S-EPMC6407429 | biostudies-literature
Project description:Recently, a growing number of evidence has revealed that long noncoding RNAs (lncRNAs) act as key regulators in various cellular biologic processes, and dysregulation of lncRNAs involves in tumorigenesis and cancer progression. However, the expression pattern, clinical relevance, and biologic function of most lncRNAs in human thyroid cancer remain unclear. To identify more thyroid-cancer-associated lncRNAs, we analyzed the expression profile of lncRNAs in thyroid cancer tissues and adjacent normal or non-tumor tissues using RNA sequencing data and gene microarray data from The Cancer Genome Atlas and Gene Expression Omnibus. Annotation and analyses of these data revealed that hundreds of lncRNAs are differentially expressed in thyroid cancer tissues when compared with normal tissues. By copy number variation analyses, we identified that some of those dysregulated lncRNAs genome locus are accompanied with the copy number amplification or deletion. Moreover, some lncRNAs expression levels are significantly associated with thyroid cancer patients overall or recurrence-free survival time, such as RUNDC3A-AS1, FOXD2-AS1, PAX8-AS1, and CRYM-AS1. Furthermore, we validated an lncRNA termed LINC00704 in thyroid cancer cells by performing loss of function assays. Downregulation of LINC00704 could significantly impair thyroid cancer cells proliferation, colony formation, inhibit cell-cycle progression and cell invasion, and induce cell apoptosis. Taken together, our findings reveal that lots of lncRNAs are dysregulated and may play critical roles in thyroid cancer, and this study could provide useful resource for identification and investigation of novel lncRNA candidates for thyroid cancer.
| S-EPMC6089163 | biostudies-literature
Project description:Distant metastasis is the main cause of breast cancer-related death; however, effective therapeutic strategies targeting metastasis are still scarce. This is largely attributable to the spatiotemporal intratumor heterogeneity during metastasis. Here we show that protein deacetylase SIRT7 is significantly downregulated in breast cancer lung metastases in human and mice, and predicts metastasis-free survival. SIRT7 deficiency promotes breast cancer cell metastasis, while temporal expression of Sirt7 inhibits metastasis in polyomavirus middle T antigen breast cancer model. Mechanistically, SIRT7 deacetylates and promotes SMAD4 degradation mediated by β-TrCP1, and SIRT7 deficiency activates transforming growth factor-β signaling and enhances epithelial-to-mesenchymal transition. Significantly, resveratrol activates SIRT7 deacetylase activity, inhibits breast cancer lung metastases, and increases survival. Our data highlight SIRT7 as a modulator of transforming growth factor-β signaling and suppressor of breast cancer metastasis, meanwhile providing an effective anti-metastatic therapeutic strategy.Metastatic disease is the major reason for breast cancer-related deaths; therefore, a better understanding of this process and its players is needed. Here the authors report the role of SIRT7 in inhibiting SMAD4-mediated breast cancer metastasis providing a possible therapeutic avenue.
| S-EPMC5566498 | biostudies-literature
Project description:BACKGROUND:NKX2.5 is a transcription factor transiently expressed during thyroid organogenesis. Recently, several works have pointed out the oncogenic role of NKX2.5 in a variety of tumors. We therefore hypothesized that NKX2.5 could also play a role in thyroid cancer. METHODS:The validation of NKX2.5 expression was assessed by immunohistochemistry analysis in a Brazilian case series of 10 papillary thyroid carcinoma (PTC) patients. Then, the long-term prognostic value of NKX2.5 and its correlation with clinicopathologic features of 51 PTC patients was evaluated in a cohort with 10-years follow-up (1990-1999). Besides, the effect of NKX2.5 overexpression on thyroid differentiation markers and function was also investigated in a non-tumor thyroid cell line (PCCL3). RESULTS:NKX2.5 was shown to be expressed in most PTC samples (8/10, case series; 27/51, cohort). Patients who had tumors expressing NKX2.5 showed lower rates of persistence/recurrence (p = 0.013). Overexpression of NKX2.5 in PCCL3 cells led to: 1) downregulation of thyroid differentiation markers (thyrotropin receptor, thyroperoxidase and sodium-iodide symporter); 2) reduced iodide uptake; 3) increased extracellular H2O2 generation, dual oxidase 1 mRNA levels and activity of DuOx1 promoter. CONCLUSIONS:In summary, NKX2.5 is expressed in most PTC samples analyzed and its presence correlates to better prognosis of PTC. In vitro, NKX2.5 overexpression reduces the expression of thyroid differentiation markers and increases ROS production. Thus, our data suggests that NKX2.5 could play a role in thyroid carcinogenesis.
| S-EPMC5930850 | biostudies-literature
Project description:BackgroundThyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed.MethodsIn this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs.ResultsWe have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs.ConclusionsExpression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.
| S-EPMC5456382 | biostudies-literature
Project description:BackgroundThe prevalence of thyroid cancer (ThyC), a frequent malignant tumor of the endocrine system, has been rapidly increasing over time. The mitophagy pathway is reported to play a critical role in ThyC onset and progression in many studies. This research aims to create a mitophagy-related survival prediction model for ThyC patients.MethodsGenes connected to mitophagy were found in the GeneCards database. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided information on the expression patterns of ThyC-related genes. To identify differentially expressed genes (DEGs), R software was employed. The prognostic significance of each DEG was assessed using the prognostic K-M curve. The prognostic model was built using LASSO, ROC, univariate, and multivariate Cox regression analyses. Finally, a nomogram model was developed to predict the survival outcome of ThyC patients in the clinical setting.ResultsThrough differential analysis, functional enrichment analysis, and protein-protein interaction (PPI) network analysis, we screened 10 key genes related to mitophagy in ThyC. The risk model was eventually developed using LASSO and Cox regression analyses based on the six DEGs related to mitophagy. An altered expression level of a mitophagy-related prognostic gene, GGCT, was found to be the most significant one, according to the KM survival curve analysis. An immunohistochemical (IHC) investigation revealed that ThyC tissues expressed higher levels of GGCT than normal thyroid tissues. The ROC curve verified the satisfactory performance of the model in survival prediction. Multivariate Cox regression analysis showed that the pathological grade, residual tumor volume, and initial tumor lesion type were significantly linked to the prognosis. Finally, we created a nomogram to predict the overall survival rate of ThyC patients at 3-, 5-, and 7- year time points.ConclusionThe nomogram risk prediction model was developed to precisely predict the survival rate of ThyC patients. The model was validated based on the most significant DEG GGCT gene expression in ThyC. This model may serve as a guide for the creation of precise treatment plans for ThyC patients.
| S-EPMC10501032 | biostudies-literature
Project description:Optimal therapeutic strategies for liver cancer patients remain challenging due to the high recurrence rate after surgical resection and chemotherapy resistance. Emerging evidence has shown that epigenetic factor SIRT7 is involved in various aspects of cancer biology, while inactive SIRT7 reverses human cancer phenotype and suppresses tumor growth. In the present study, we predicted the SIRT7 structure by using the fold recognition (or threading) method and performed structure-based virtual screening to develop specific SIRT7 inhibitor by docking 939319 structurally diverse compounds with SIRT proteins. Compounds with high affinities to SIRT7 but low affinities to other SIRT proteins were chosen as candidates of specific SIRT7 inhibitor. Our leading compounds 2800Z and 40569Z showed strong interaction with SIRT7 protein, and specifically inhibited SIRT7 deacetylation activity in vitro. Our docking results also revealed that ARG-120, TRP-126, and HIS-187 were critical sites responsible for interaction of SIRT7 with small molecules. Mutations in the aforementioned sites significantly abolished interaction and inhibitory effects of compounds to SIRT7. In addition, in vivo data indicated that compounds 2800Z and 40569Z were able to induce apoptosis and increase chemosensitivity to sorafenib in human liver cancer. Our findings demonstrated targeting SIRT7 may offer novel therapeutic options for cancer management, and the value of compounds 2800Z and 40569Z as chemical probes for the study of SIRT7 biological functions as well as starting leads for the development of new therapeutic options against liver cancer.
| S-EPMC8841758 | biostudies-literature