scholarly journals MicroRNA Deregulation in Anaplastic Thyroid Cancer Biology

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Cesar Seigi Fuziwara ◽  
Edna Teruko Kimura
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cancer Progression ◽  
Cell Biology ◽  
Cancer Biology ◽  
Anaplastic Thyroid Cancer ◽  
Genetic Alterations ◽  
Thyroid Tumor ◽  
Mesenchymal Transition ◽  
Promising Therapeutic Approach

Anaplastic thyroid cancer (ATC) is among the most lethal types of cancers, characterized as a fast-growing and highly invasive thyroid tumor that is unresponsive to surgery and radioiodine, blunting therapeutic efficacy. Classically, genetic alterations in tumor suppressorTP53are frequent, and cumulative alterations in different signaling pathways, such as MAPK and PI3K, are detected in ATC. Recently, deregulation in microRNAs (miRNAs), a class of small endogenous RNAs that regulate protein expression, has been implicated in tumorigenesis and cancer progression. Deregulation of miRNA expression is detected in thyroid cancer. Upregulation of miRNAs, such asmiR-146b,miR-221, andmiR-222, is observed in ATC and also in differentiated thyroid cancer (papillary and follicular), indicating that these miRNAs’ overexpression is essential in maintaining tumorigenesis. However, specific miRNAs are downregulated in ATC, such as those of themiR-200andmiR-30families, which are important negative regulators of cell migration, invasion, and epithelial-to-mesenchymal transition (EMT), processes that are overactivated in ATC. Therefore, molecular interference to restore the expression of tumor suppressor miRNAs, or to blunt overexpressed oncogenic miRNAs, is a promising therapeutic approach to ameliorate the treatment of ATC. In this review, we will explore the importance of miRNA deregulation for ATC cell biology.

scholarly journals Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 367 ◽  
Author(s):  
Melnik ◽  
Sahana ◽  
Corydon ◽  
Kopp ◽  
Nassef ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Signal Pathways ◽  
Dependent Manner ◽  
Spheroid Formation ◽  
Mesenchymal Transition

Detachment and the formation of spheroids under microgravity conditions can be observed with various types of intrinsically adherent human cells. In particular, for cancer cells this process mimics metastasis and may provide insights into cancer biology and progression that can be used to identify new drug/target combinations for future therapies. By using the synthetic glucocorticoid dexamethasone (DEX), we were able to suppress spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells that were exposed to altered gravity conditions on a random positioning machine. DEX inhibited the growth of three-dimensional cell aggregates in a dose-dependent manner. In the first approach, we analyzed the expression of several factors that are known to be involved in key processes of cancer progression such as autocrine signaling, proliferation, epithelial–mesenchymal transition, and anoikis. Wnt/β-catenin signaling and expression patterns of important genes in cancer cell growth and survival, which were further suggested to play a role in three-dimensional aggregation, such as NFKB2, VEGFA, CTGF, CAV1, BCL2(L1), or SNAI1, were clearly affected by DEX. Our data suggest the presence of a more complex regulation network of tumor spheroid formation involving additional signal pathways or individual key players that are also influenced by DEX.

scholarly journals Osteopontin Expression in Thyroid Cancer: Deciphering EMT-Related Molecular Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1372
Author(s):  
Bruna Prunes Pena Baroni Viana ◽  
Amanda Vitória Pampolha Gomes ◽  
Etel Rodrigues Pereira Gimba ◽  
Luciana Bueno Ferreira
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Endocrine System ◽  
Good Prognosis ◽  
Thyroid Tumor ◽  
Diagnostic Tools ◽  
Matricellular Protein ◽  
Mesenchymal Transition

Thyroid cancer is the most common tumor arising from the endocrine system and generally presents good prognosis. However, its aggressive subtypes are related to therapeutic resistance and early metastasis. Epithelial–mesenchymal transition (EMT) and its reverse process, the mesenchymal–epithelial transition (MET), are key events mediating cancer progression, including in thyroid cancer. The matricellular protein osteopontin (OPN) has been reported as a master regulator of EMT in many tumor types. Although high OPN expression has been described and associated with important aspects of thyroid cancer progression, there is no clear evidence regarding OPN as a regulator of EMT in thyroid cancer. Thus, taking together the known roles of OPN in the modulation of EMT in cancer and the information reporting the expression of OPN in thyroid tumor progression, this review aims at summarizing and discussing data related to EMT in thyroid cancer and its putative relation to the roles of OPN in the development of thyroid cancer. These data provide new insights into the molecular mechanisms by which OPN could potentially modulate EMT in thyroid tumors, generating evidence for future studies that may contribute to new therapeutic, prognostic and/or diagnostic tools.

scholarly journals Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

2015 ◽  
Vol 23 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Jeong Won Park ◽  
Cho Rong Han ◽  
Li Zhao ◽  
Mark C Willingham ◽  
Sheue-yann Cheng
Keyword(s):  
Thyroid Cancer ◽  
Mouse Model ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Specific Inhibitor ◽  
Epidemiologic Studies ◽  
Thyroid Tumor ◽  
Obesity Prevalence ◽  
Marked Rise ◽  
Mesenchymal Transition

Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (ThrbPV/PVPten+/− mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD-induced aggressive cancer progression in the mouse model of thyroid cancer. WT and ThrbPV/PVPten+/− mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition (EMT). S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase 4 (CDK4), CDK6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated ThrbPV/PVPten+/− mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated ThrbPV/PVPten+/− mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of EMT. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer.

scholarly journals A New Aurora in Anaplastic Thyroid Cancer Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Enke Baldini ◽  
Massimino D’Armiento ◽  
Salvatore Ulisse
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Human Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Malignant Cell ◽  
Thyroid Tumor ◽  
Antitumor Effects ◽  
Aurora Kinases ◽  
Mitotic Kinases ◽  
Human Cancers

Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation.

scholarly journals Long non-coding RNA TUSC7 suppressed colorectal cancer progression via regulation of miR-23b/PDE7A Axis

2020 ◽  
Vol 43 (4) ◽  
pp. E35-43
Author(s):  
Lingfang Hao ◽  
Yaofeng Yun ◽  
Run Liang ◽  
Gang Yuan
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Progression

Purpose: Despite advances in our understanding of the roles of the long noncoding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) in cancer biology, which has been identified to act as a tumor suppressor by regulating cell proliferation, apoptosis, migration, invasion, cell cycle and tumor growth, its function in colorectal cancer remains unknown. Methods: The expression levels of TUSC7 in colorectal cancer tissues and cell lines were determined, and the biological functions of TUSC7 to cancer progression in colorectal cancer were investigated via correlation analysis of clinical samples, cell viability assay, transwell assay and apoptosis analysis. Further, the molecular regulatory mechanisms of TUSC7 were demonstrated by luciferase reporter assay and western blotting. Results: We observed that the expression of TUSC7 was markedly decreased in colorectal cancer cell lines. Moreover, the lower expression of TUSC7 was correlated with advanced clinical grades and poorer survival and may be an independent risk factor for colorectal cancer. Moreover, the expression of TUSC7 inhibited cell proliferation, invasion and epithelial-to-mesenchymal transition (EMT), while it facilitated apoptosis through competitively binding miR-23b. We also found that TUSC7 decreased the expression of phosphodiesterase 7A (PDE7A), a downstream target of miR-23b, through the TUSC7/miR-23b/PDE7A axis. Conclusion: We demonstrated the expression of TUSC7 suppressed colorectal cancer progression through the TUSC7/miR-23b/PDE7A axis, suggesting that TUSC is a potential target for therapeutic intervention in colorectal cancer.

scholarly journals Exploring Hyperoxia Effects in Cancer—From Perioperative Clinical Data to Potential Molecular Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1213
Author(s):  
Anca Irina Ristescu ◽  
Crina Elena Tiron ◽  
Adrian Tiron ◽  
Ioana Grigoras
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Experimental Studies ◽  
Perioperative Period ◽  
Postoperative Recovery ◽  
Mesenchymal Transition ◽  
Oncological Treatment

Increased inspiratory oxygen concentration is constantly used during the perioperative period of cancer patients to prevent the potential development of hypoxemia and to provide an adequate oxygen transport to the organs, tissues and cells. Although the primary tumours are surgically removed, the effects of perioperative hyperoxia exposure on distal micro-metastases and on circulating cancer cells can potentially play a role in cancer progression or recurrence. In clinical trials, hyperoxia seems to increase the rate of postoperative complications and, by delaying postoperative recovery, it can alter the return to intended oncological treatment. The effects of supplemental oxygen on the long-term mortality of surgical cancer patients offer, at this point, conflicting results. In experimental studies, hyperoxia effects on cancer biology were explored following multiple pathways. In cancer cell cultures and animal models, hyperoxia increases the production of reactive oxygen species (ROS) and increases the oxidative stress. These can be followed by the induction of the expression of Brain-derived neurotrophic factor (BDNF) and other molecules involved in angiogenesis and by the promotion of various degrees of epithelial mesenchymal transition (EMT).

scholarly journals CircPLEKHM3 acts as a tumor suppressor through regulation of the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis in ovarian cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Lei Zhang ◽  
Qing Zhou ◽  
Qiongzi Qiu ◽  
Ling Hou ◽  
Mengting Wu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Biology ◽  
Ovarian Cancer Cells ◽  
Ovarian Carcinomas ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Endogenous Expression

Abstract Background Emerging evidence has shown that circular RNAs (circRNAs) play essential roles in cancer biology and are potential biomarkers and targets for cancer therapy. However, the expression and function of circRNAs in ovarian carcinogenesis and its progression remain elusive. Methods RNA sequencing was performed to reveal circRNA expression profiles in ovarian cancerous and normal tissues. Single-molecule RNA in-situ hybridization was used to quantify circPLEKHM3 expression in tumor tissues. Cell-based in-vitro and in-vivo assays were subsequently conducted to support the clinical findings. Results CircPLEKHM3 was identified as one of the most significantly down-regulated circRNAs in ovarian cancer tissues compared with normal tissues. Its expression was further decreased in peritoneal metastatic ovarian carcinomas compared to primary ovarian carcinomas. Patients with lower circPLEKHM3 tend to have a worse prognosis. Functionally, circPLEKHM3 overexpression inhibited cell growth, migration and epithelial–mesenchymal transition, whereas its knockdown exerted an opposite role. Further analyses showed that circPLEKHM3 sponged miR-9 to regulate the endogenous expression of BRCA1, DNAJB6 and KLF4, and consequently inactivate AKT1 signaling. In addition, AKT inhibitor MK-2206 could block the tumor-promoting effect of circPLEKHM3 depletion, and potentiate Taxol-induced growth inhibition of ovarian cancer cells. Conclusions Our findings demonstrated that circPLEKHM3 functions as a tumor suppressor in ovarian cancer cells by targeting the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis and may be used as a prognostic indicator and therapeutic target in ovarian cancer patients. The new strategy for treating ovarian cancer by a combination therapy of Taxol with MK-2206 is worth further investigation, especially in ovarian cancer patients with loss of circPLEKHM3 expression.

Abstract 4367: Tumor suppressor miR-30a inhibits LOX expression and progression in anaplastic thyroid cancer

2014 ◽  
Author(s):  
Myriem Boufraqech ◽  
Naris Nilubol ◽  
Lisa Zhang ◽  
Samira Sadowski ◽  
Sudheer Kumar Gara ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Anaplastic Thyroid Cancer
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