Thymosin β10 Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production

Kim, Young-Chae; Kim, Byoung-Gie; Lee, Je‐Ho

doi:10.1371/journal.pone.0035399

Cited by 19 publications

(15 citation statements)

References 54 publications

(38 reference statements)

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“…TMSB10 is upregulated in multiple human cancers and upregulation of TMSB10 contributes to cancer cell proliferation, migration and invasion via different mechanisms, and predicts poor survival [ 13 , 15 , 31 – 33 ]. However, the expression of TMSB10 has also been shown to be downregualted in ovarian cancer tissues and cells and overexpression of TMSB10 diminishes tumor growth and proliferation [ 34 , 35 ]. These findings indicate that TMSB10 functions as both an oncogenic and tumor-suppressive gene depending on the tumor type.…”

Section: Discussionmentioning

confidence: 99%

Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer

et al. 2017

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BackgroundThymosin beta 10 (TMSB10) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to determine the biological roles and clinical significance of TMSB10 in breast cancer and to identify whether TMSB10 might be used as a serum marker for the diagnosis of breast cancer.MethodsTMSB10 expression was evaluated by immunohistochemical analysis (IHC) of 253 breast tumors and ELISA of serum from 80 patients with breast cancer. Statistical analysis was performed to explore the correlation between TMSB10 expression and clinicopathological features in breast cancer. Univariate and multivariate Cox regression analysis were performed to examine the association between TMSB10 expression and overall survival and metastatic status. In vitro and in vivo assays were performed to assess the biological roles of TMSB10 in breast cancer. Western blotting and luciferase assays were examined to identify the underlying pathway involved in the tumor-promoting role of TMSB10.ResultsWe found TMSB10 was upregulated in breast cancer cells and tissues. Univariate and multivariate analysis demonstrated that high TMSB10 expression significantly correlated with clinicopathological features, poor prognosis and distant metastases in patients with breast cancer. Overexpression of TMSB10 promotes, while silencing of TMSB10 inhibits, proliferation, invasion and migration of breast cancer cells in vitro and in vivo. Our results further reveal that TMSB10 promotes the proliferation, invasion and migration of breast cancer cells via AKT/FOXO signaling, which is antagonized by the AKT kinase inhibitor perifosine. Importantly, the expression of TMSB10 is significantly elevated in the serum of patients with breast cancer and is positively associated with clinical stages of breast cancer.ConclusionTMSB10 may hold promise as a minimally invasive serum cancer biomarker for the diagnosis of breast cancer and a potential therapeutic target which will facilitate the development of a novel therapeutic strategy against breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0785-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer

et al. 2017

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“…In contrast, results showed downregulation of TMSB10 that regulates actin dynamics as a cytoplasm G-actin-sequestering protein leading to actin disruption and apoptosis in cancer cells. 22 In addition, the protein encoded by SSH1 gene dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly; 23 this gene is down-regulated in SPARC −/− mice. Another important gene found downregulated is TNFRSF14 , a member of the TNF-receptor super-family, which may mediate the signal transduction pathways that activate the immune response triggered by Con A administration.…”

Section: Discussionmentioning

confidence: 99%

SPARC (secreted protein acidic and rich in cysteine) knockdown protects mice from acute liver injury by reducing vascular endothelial cell damage

et al. 2014

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Secreted protein, acidic and rich in cysteine (SPARC) is involved in many biological process including liver fibrogenesis, but its role in acute liver damage is unknown. To examine the role of SPARC in acute liver injury, we used SPARC knock-out (SPARC−/−) mice. Two models of acute liver damage were used: concanavalin A (Con A) and the agonistic anti-CD95 antibody Jo2. SPARC expression levels were analyzed in liver samples from patients with acute-on-chronic alcoholic hepatitis (AH). SPARC expression is increased on acute-on-chronic AH patients. Knockdown of SPARC decreased hepatic damage in the two models of liver injury. SPARC−/− mice showed a marked reduction in Con A-induced necroinflammation. Infiltration by CD4+ T cells, expression of tumor necrosis factor-α and interleukin-6 and apoptosis were attenuated in SPARC−/− mice. Sinusoidal endothelial cell monolayer was preserved and was less activated in Con A-treated SPARC−/− mice. SPARC knockdown reduced Con A-induced autophagy of cultured human microvascular endothelial cells (HMEC-1). Hepatic transcriptome analysis revealed several gene networks that may have a role in the attenuated liver damaged found in Con A-treated SPARC−/− mice. SPARC has a significant role in the development of Con A-induced severe liver injury. These results suggest that SPARC could represent a therapeutic target in acute liver injury.

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“…Cancer-specific promoters, such as the promoter of the telomerase gene, are active specifically in cancerous cells and minimize transgene expression in normal cells 100,101 . Ligand-directed targeting is a more popular choice to delivery transgene specifically to cancerous cells that express corresponding receptors on their surface.…”

Section: Delivery Of Crispr-cas9 System To Cancer Cellsmentioning

confidence: 99%

CRISPR/Cas9-Mediated Genome Editing of Epigenetic Factors for Cancer Therapy

Yao

Chen

2015

Human Gene Therapy

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Advances in engineered recombinant nuclease have provided facile and reliable methods for genome editing. Especially with the development of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) system, the discovery of various versions of Cas9 proteins and delivery carriers, it is now practicable to introduce desired mutations into the genome, to correct disease-related mutations, and to activate or suppress genes of interest. Epigenetic regulators are often disturbed in cancer cells and are essential for the transformation of normal to cancerous cells. Tumor-related epigenetic alterations or epigenetic factor mutations play a major part during the various steps of carcinogenesis and affect a variety of cancer-related genes and a wide range of cancerous phenotypes. Therefore, epigenetic regulatory enzymes might be candidate targets for cancer therapy. In this review, we discuss prospects of CRISPR/Cas9-based genome editing in targeting epigenetics for cancer gene therapy.

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Thymosin β10 Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production

Cited by 19 publications

References 54 publications

Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer

Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer

SPARC (secreted protein acidic and rich in cysteine) knockdown protects mice from acute liver injury by reducing vascular endothelial cell damage

CRISPR/Cas9-Mediated Genome Editing of Epigenetic Factors for Cancer Therapy

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