Edna T Kimura

• MD. PhD. - Professor
• Professor (Full) at University of São Paulo

Introduction Anaplastic thyroid cancer (ATC) is a rare but highly aggressive endocrine malignancy characterized by rapid tumor growth, early metastasis (>40%), and resistance to standard therapies like radioiodine. The epithelial-mesenchymal transition (EMT) is a critical process driving ATC progression and metastasis, underscoring the urgency of i...

Modulating the expression of a coding or noncoding gene is a key tool in scientific research. This strategy has evolved methodologically due to advances in cloning approaches, modeling/algorithms in short hairpin RNA (shRNA) design for knockdown efficiency, and biochemical modifications in RNA synthesis, among other developments. Overall, these mod...

Background In previous studies, we demonstrated the downregulation of several miRNAs from the DLK1-DIO3 genomic region in papillary thyroid carcinoma (PTC). Due to the large number of miRNAs within this region, the individual contribution of these molecules to PTC development and progression remains unclear. Objective In this study, we aimed to cl...

Thyroid cancer is the most prevalent endocrine malignancy, comprising multiple types of cancer, with distinct clinical-pathological characteristics. The oncogenesis of thyroid cancer is related to genetic alterations in MAPK signaling that induce proliferation and modulate noncoding genes, such as microRNAs and long noncoding RNAs. In this context,...

Anaplastic thyroid cancer (ATC) is a rare and lethal form of thyroid cancer that requires urgent investigation of new molecular targets involved in its aggressive biology. In this context, the overactivation of Polycomb Repressive Complex 2/EZH2, which induces chromatin compaction, is frequently observed in aggressive solid tumors, making the EZH2...

Anaplastic Thyroid Cancer (ATC) is the most aggressive and lethal of all thyroid cancer histotypes, characterized by undifferentiated, highly proliferative and invasive cells, which are intrinsically resistant to conventional treatment. Deregulation of microRNAs (miRNAs), a group of small non-coding RNAs that post-transcriptionally regulates protei...

Simple Summary Papillary thyroid cancer is not an aggressive cancer, even when metastasis are present; therefore, treatment has been downgraded in recent years. However rare, mortality exists and finding the factors associated with mortality is essential and has not yet been fully accomplished; the answer probably lies in molecular factors. This st...

Desenvolvido pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM), o Guia Prático em Doenças da Tireoide está integrado ao rol de materiais de divulgação científica e educação médica lançados pela instituição nos últimos anos. Em 28 capítulos elaborados por professores, pesquisadores e endocrinologistas com r...

Introduction: Anaplastic thyroid cancer (ATC) is a rare and lethal undifferentiated thyroid malignancy, with rapid growth, invasion of adjacent tissues and distant metastasis (>50% of cases), leading to survival of ~ 6 months. Understanding the molecular evolution of ATC is a current challenge in thyroid cancer field that may lead to identification...

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are essential players in the regulation of gene expression. The majority of the twenty different hnRNP proteins act through the modulation of pre‐mRNA splicing. Most have been shown to regulate the expression of critical genes for the progression of tumorigenic processes and were also observed to be...

Knockout (ko) mice for the β2 adrenoceptor (Adrβ2) have impaired skeletal muscle regeneration, suggesting that this receptor is important for muscle stem cell (satellite cell) function. Here, we investigated the role of Adrβ2 in the function of satellite cells from β2ko mice in the context of muscle regeneration, through in vivo and in vitro experi...

Knockout (ko) mice for the β2 adrenoceptor (Adrβ2) have impaired skeletal muscle regeneration, suggesting that this receptor is important for muscle stem cell (satellite cell) function. Here, we investigated the role of Adrβ2 in the function of satellite cells from β2ko mice in the context of muscle regeneration, through in vivo and in vitro experi...

The presence of a bidirectional risk for metachronous carcinomas among women with thyroid and breast cancer is well established. However, the underlying risk factors remain poorly understood. Two sisters developed papillary thyroid cancer (PTC) at age 32 and 34 years, followed by ductal carcinoma of the breast at 44 and 42 years. The two children o...

Simple Summary The advent of genomic editing with CRISPR/Cas9 has transformed the way we manipulate the genome, and has facilitated the investigation of tumor cell biology in vitro and in vivo. Not only we can modify genome sequence to blunt an overactivated gene or correct a mutation, but also we may modulate gene expression using CRISPR/Cas syste...

Thyroid cancer is the most common endocrine malignancy, and the characterization of the genetic alterations in coding-genes that drive thyroid cancer are well consolidated in MAPK signaling. In the context of non-coding RNAs, microRNAs (miRNAs) are small non-coding RNAs that, when deregulated, cooperate to promote tumorigenesis by targeting mRNAs,...

Purpose: Ciliary epithelium (CE) of adult mammalian eyes contains quiescent retinal progenitor/stem cells that generate neurospheres in vitro and differentiate into retinal neurons. This ability doesn't evolve efficiently probably because of regulatory mechanisms, such as microRNAs (miRNAs) that control pluripotent, progenitor, and differentiation...

Vitreous alterations occur from early stages and continue through the normal aging, with gradual lamellae formation and the appearance of liquefied spaces, which eventually leads to complications, such as retinal tear, retinal detachment, and intravitreal hemorrhage. The aim of the present study was to investigate the expression of let-7 miRNA fami...

Background: DLK1-DIO3 genomic region comprises one of the largest microRNA (miRNAs) clusters in human genome. In previous studies we showed the downregulation of several miRNAs from the genomic region in papillary thyroid carcinoma (PTC). Due to the large number of miRNAs within this region the individual contribution of these molecules to PTC deve...

Thyroid cancer is the most frequent endocrine malignancy with the majority of cases derived from thyroid follicular cells and caused by sporadic mutations. However, when at least two or more first degree relatives present thyroid cancer, it is classified as familial non-medullary thyroid cancer (FNMTC) that may comprise 3–9% of all thyroid cancer....

Oral cancer squamous cell carcinoma (OCSCC) mainly affects individuals aged between 50 and 70 years who consume tobacco and alcohol. Tobacco smoke contains hundreds of known toxic and carcinogenic molecules, and a few studies have sought to verify the relationship of such trace elements as risk or prognostic factors for head and neck cancer. We obt...

Background: Loss of the expression of thyroid differentiation markers such as NIS and, consequently, radioiodine refractoriness is observed in aggressive papillary and anaplastic thyroid cancers that may harbor the BRAFV600E mutation. Activation of the BRAFV600E oncogene in thyroid follicular cells induces the expression of the miR-17-92 cluster t...

Thyroid cancer has been rapidly increasing in prevalence among humans in last 2 decades and is the most prevalent endocrine malignancy. Overall, thyroid-cancer patients have good rates of long-term survival, but a small percentage present poor outcome. Thyroid cancer aggressiveness is essentially related with thyroid follicular cell loss of differe...

TCGA genomic study in papillary thyroid carcinoma (PTC) samples highlights two groups of tumors: BRAF-like and -like, whose genotype might influence its biological behavior. The mechanisms behind progressive loss of thyroid differentiation, observed mainly in the most aggressive histotype anaplastic thyroid carcinoma (ATC), could be associated with...

TCGA genomic study in papillary thyroid carcinoma (PTC) samples highlights two groups of tumors: BRAF-like and -like, whose genotype might influence its biological behavior. The mechanisms behind progressive loss of thyroid differentiation, observed mainly in the most aggressive histotype anaplastic thyroid carcinoma (ATC), could be associated with...

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 molecula...

(A) Imunodetection of FAM83F using an anti Myc-tag antibody and secondary antibody conjugated with Alexa Fluor 488 by imunofluorescence. Green fluorescence indicates the presence of FAM83F expression. (B) Wound-healing assay for migration analysis: Cell migration was enhanced in PCCL3-FAM83F compared to PCCL3-Φ cells shown by wound closure after 8...

Oligonucleotides used for qPCR.

(A) FAM83F gene expression in different types of cancer extracted from TCGA database via cBioportal website. (B) FAM83F gene expression; (C) miR-143, and (D) miR-455 gene expression in a cohort of 60 PTC patients extracted from TCGA database as described previously (21). *P < 0.01 vs. non-tumoral, ***P < 0.001 vs. non-tumoral using Mann-Whitney tes...

Several studies have demonstrated dysregulated cardiac microRNAs (miRNAs) following cardiac stress and development of cardiac hypertrophy and failure. miRNAs are also differentially expressed in the inflammation that occurs in heart failure and, among these inflammatory-related miRNAs, the miR-155 has been implicated in the regulation of cardiac hy...

Emerging evidence suggests that unregulated Toll-like receptor (TLR) signaling promotes tumor survival signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillary thyroid carcinomas (PTC) mainly harboring the BRAFV600Emutation was studied. TLR4 was overexpressed in PTC compared with nonneoplastic thyroi...

BACKGROUND: Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenti...

Background: Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, present...

Skeletal myogenesis is a regulated process in which mononucleated cells, the myoblasts, undergo proliferation and differentiation. Upon differentiation, the cells align with each other, and subsequently fuse to form terminally differentiated multinucleated myotubes. Previous reports have identified the protein osteoglycin (Ogn) as an important comp...

Experimental design and lipofectamine treatment. (PDF)

miR-155 alignment sequence in different species. (PDF)

Geoprofile dataset. (PDF)

Oligonucleotides segment containing the miR-155 binding site on Ogn 3’UTR predicted by TargetScan algorithm. (PDF)

Genes and primer sequences used in RT-qPCR. (PDF)

Reference genes used in RT-qPCR. (PDF)

Background: Thyroid cancer is one of the most frequent types of endocrine cancers. In most cases, thyroid cancers are caused by deregulated miRNA expression, especially involving the miR17-92 cluster. miR17-92 transcription is altered in several different tumor types including lymphoma, leukemia, and of the breast and thyroid. As an intronic clust...

Papillary Thyroid Cancer (PTC) is an endocrine malignancy in which BRAFV600E oncogenic mutation induces the most aggressive phenotype. In this way, considering that lncRNAs are arising as key players in oncogenesis, it is of high interest the identification of BRAFV600E-associated long noncoding RNAs, which can provide possible candidates for secon...

Papillary thyroid carcinoma (PTC) is the most prevalent malignant neoplasia of the thyroid gland. A fraction of PTC cases show loss of differentiation and aggressive behavior, with radioiodine therapy resistance and metastasis. Although microRNAs (miRNAs) emerged as promising molecular markers for PTC, their role in the loss of differentiation obse...

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that modulate the vast majority of cellular processes. During development, the correct timing and expression of miRNAs in the tissue differentiation is essential for organogenesis and functionality. In thyroid gland, DICER and miRNAs are necessary for accurately est...

Nose is the first portion of the respiratory system into contact with air pollution particles, including organic compounds that could act as endocrine releasers. The objective was to identify and quantify estrogenic receptor-β (ERβ), aryl hydrocarbon receptor (AhR), the cytochrome P450 enzymes CYP1A1, 1A2, 1B1, and mucus profile in the nasal epithe...

Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic Q2 disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in human PTC cell lines (K1 an...

Background: The analyses of several systems for medical-imaging processing typically support the extraction of image attributes, but do not comprise some information that characterizes images. For example, morphometry can be applied to find new information about the visual content of an image. The extension of information may result in knowledge....

Background Tumor invasiveness is directly related to the ability of tumor cells to migrate and invade surrounding tissues, usually degrading extracellular matrix. Despite significant progress in the knowledge about migration and invasion, there is much more to elucidate about their regulatory mechanisms, especially in cancer cells. MicroRNAs (miRs)...

Papillary thyroid carcinoma (PTC) is a well-differentiated thyroid tumor that accounts for approximately 80% of thyroid cancer cases. On other hand, anaplastic thyroid carcinoma (ATC) is a less frequent, but aggressive subtype, with poor prognosis. MicroRNAs (miRNAs), small non-coding RNAs, have emerged as potent post-transcriptional regulators of...

Overexpression of the miR-17-92 cluster is a key oncogenic event in various cancer types. The oncogenic effect of the miR-17-92 cluster is enhanced by cooperation between its members in targeting tumor-suppressive proteins and pathways such as PTEN and TGFβ signaling. However, in the case of miR-19a and miR-19b, these have been shown to have a prep...

Thyroid hormone (TH) signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs); THRα1 and THRβ1. We aimed to investigate the regulation mechanisms of the THRβ isoform, its association with gene expression changes and implications for cardiac function. The experiments were performed using adult male mice express...

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Thyroid follicular cells proliferation is regulated by TGFβ anti-mitogenic signal. However, thyroid cancer cells become refractory to this inhibitory signal. TGFβ signaling deregulation is observed in thyroid cancer, which shows high frequence of MAPK genetic alterat...

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 suppressor TP53 are frequent, and cumulative alterations in different signaling pathway...

As life expectancy increases, the occurrence of cancer as a cause of mortality and morbidity becomes increasingly more relevant. Thyroid cancer is the most frequent endocrine malignancy, and worldwide incidence is rapidly increasing. Among different follicular thyroid cell-derived cancers, the papillary histotype is the most frequent, as well as be...

About one half of malignant peripheral nerve sheath tumors (MPNST) have Neurofibromin 1 (NF1) mutations. NF1 is a tumor suppressor gene essential for negative regulation of RAS signaling. Survival for MPNST patients is poor and we sought to identify an effective combination therapy. Starting with the mTOR inhibitors rapamycin and everolimus, we scr...

Introduction: Papillary thyroid carcinoma (PTC) is a well differentiated tumor that accounts for more than 80% of the thyroid cancer cases. Although PTC presents good prognosis, about 5% of the cases present a more aggressive behavior, evolving to poorly differentiated thyroid carcinoma (PDTC) and becoming refractory to chemo and radioiodine therap...

Background: Excess iodine inhibits thyroid follicular cell proliferation associated with TGFβ pathway activation, although thyroid cancers are frequently refractory to TGFβ signaling. The TGFβ pathway is predicted to be regulated by miR-17-92 cluster microRNAs. MicroRNAs are small noncoding RNAs that inhibit target mRNA translation and have emerge...

Background: BRAF mutation (T1799A) is the most prevalent genetic alteration in thyroid malignancy, associated with aggressive and poor prognosis thyroid cancer. Iodine excess exerts anti-proliferative effects in thyroid cells associated to TGFβ pathway enhancement, although refractoriness to TGFβ inhibitory signal is observed in thyroid cancer. We...

Mutually exclusive genetic alterations in the RET, RAS, or BRAF genes, which result in constitutively active mitogen-activated protein kinase (MAPK) signaling, are present in about 70% of papillary thyroid carcinomas (PTCs). However, the effect of MAPK activation on other signaling pathways involved in oncogenic transformation, such as Notch, remai...

Triiodotironine (T3) is critical for cardiac function. Heart expresses TRα1 e TRβ1, the two main thyroid hormone (TH) receptors (TR). We aimed to investigate the role of TRβ1 on T3‐induced cardiac hypertrophy. Adult male mice, wild‐type (WT) or homozygous (HO) for Δ337T mutation on TRβ (unable to bind T3), were used. Animals were studied at baselin...

O hipotireoidismo congênito (HC) é o distúrbio endócrino congênito mais frequente, com incidência variando de 1:2.000 a 1:4.000 crianças nascidas vivas e uma das principais causas de retardo mental que pode ser prevenida. Os Programas de Triagem Neonatal para a doença permitem a identificação precoce dos afetados e seu tratamento de modo a evitar a...

In cancer, microRNAs dysregulation affects the post-transcriptional control of oncogenes and tumor suppressors. Let-7 importance emerged in cancer when its implication in regulating the expression of RAS oncogene family was uncovered. Frequently reduced in several types of cancer, Let-7 exerts a tumor suppressor role in tumorigenesis, and loss of i...

Papillary thyroid cancer (PTC) is the most incident histotype of thyroid cancer. A certain fraction of PTC cases (5%) are irresponsive to conventional treatment, and refractory to radioiodine therapy. The current prognostic factors for aggressiveness are mainly based on tumor size, the presence of lymph node metastasis, extrathyroidal invasion and,...

Background: RET/PTC, RAS and BRAF are present in about two thirds of papillary thyroid carcinomas (PTC), activating constitutively the mitogen activated protein kinase (MAPK) signaling pathway. There is practically no overlap between RET/PTC, RAS and BRAF mutations in PTC, the lack of concordance for these mutations provides compelling genetic evid...

The spleen plays a crucial role in the development of immunity to malaria, but the role of pattern recognition receptors (PRRs) in splenic effector cells during malaria infection is poorly understood. In the present study, we analysed the expression of selected PRRs in splenic effector cells from BALB/c mice infected with the lethal and non-lethal...

Background: High dose iodine intake is used as a prophylactic measure to protect thyroid from deleterious effects of radioactive iodine in case of nuclear accidents. In vitro, high concentration iodine delays oncogenic effects of RET/PTC3 in thyroid follicular cells, although its role during BRAF oncogene activation remains unclear. BRAF mutation (...

The phenomenon that supraphysiological doses of iodide (I(-)) temporarily inhibit thyroid hormone synthesis is known as thyroid iodide autoregulation. Recovery of thyroid function has been attributed to sodium-iodide symporter (NIS) inhibition, but the diversity of available data makes it difficult to reach definitive conclusions. Iodide excess ind...

MicroRNAs (miRNA) are small non-coding RNAs involved in post-transcriptional gene regulation that have crucial roles in several types of tumors, including papillary thyroid carcinoma (PTC). miR-146b-5p is overexpressed in PTCs and is regarded as a relevant diagnostic marker for this type of cancer. A computational search revealed that miR-146b-5p p...

Background: Angiotensin II (AngII) exerts promitotic, pro-proliferative and angiogenic effects and the administration of angiotensin I-converting enzyme (ACE) inhibitors reduces tumor growth in animal models of cancer. AngII type 1 receptor (AGTR1) is found in a wide variety of normal tissues, increased expression is often found in the correspondin...

To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-beta/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-beta and activin, while SMAD7 inhibits this intracellular...

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy and RET/PTC rearrangements represent key genetic events frequently associated to this cancer, enhancing proliferation and dedifferentiation by activation of the RET/PTC-RAS-BRAF-mitogen-activated protein kinase (MAPK) pathway. Recently, let-7 microRNA was found to reduce RAS...

Papillary thyroid carcinoma (PTC) is frequently associated with a RET gene rearrangement that generates a RET/PTC oncogene. RET/PTC is a fusion of the tyrosine kinase domain of RET to the 5' portion of a different gene. This fusion results in a constitutively active MAPK pathway, which plays a key role in PTC development. The RET/PTC3 fusion is pri...

We developed mice with germline endogenous expression of oncogenic Hras to study effects on development and mechanisms of tumor initiation. They had high perinatal mortality, abnormal cranial dimensions, defective dental ameloblasts, and nasal septal deviation, consistent with some of the features of human Costello syndrome. These mice developed pa...