scholarly journals Effects of Anti-Cancer Drug Sensitivity-Related Genetic Differences on Therapeutic Approaches in Refractory Papillary Thyroid Cancer

2022 ◽  
Vol 23 (2) ◽  
pp. 699
Author(s):  
Hyeok Jun Yun ◽  
Minki Kim ◽  
Sang Yong Kim ◽  
Sungsoon Fang ◽  
Yonjung Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Combination Therapy ◽  
Papillary Thyroid Cancer ◽  
Thyroid Tissue ◽  
Cancer Drug ◽  
Papillary Thyroid ◽  
Anti Cancer ◽  
Well Differentiated

Thyroid cancer (TC) includes tumors of follicular cells; it ranges from well differentiated TC (WDTC) with generally favorable prognosis to clinically aggressive poorly differentiated TC (PDTC) and undifferentiated TC (UTC). Papillary thyroid cancer (PTC) is a WDTC and the most common type of thyroid cancer that comprises almost 70–80% of all TC. PTC can present as a solid, cystic, or uneven mass that originates from normal thyroid tissue. Prognosis of PTC is excellent, with an overall 10-year survival rate >90%. However, more than 30% of patients with PTC advance to recurrence or metastasis despite anti-cancer therapy; consequently, systemic therapy is limited, which necessitates expansion of improved clinical approaches. We strived to elucidate genetic distinctions due to patient-derived anti-cancer drug-sensitive or -resistant PTC, which can support in progress novel therapies. Patients with histologically proven PTC were evaluated. PTC cells were gained from drug-sensitive and -resistant patients and were compared using mRNA-Seq. We aimed to assess the in vitro and in vivo synergistic anti-cancer effects of a novel combination therapy in patient-derived refractory PTC. This combination therapy acts synergistically to promote tumor suppression compared with either agent alone. Therefore, genetically altered combination therapy might be a novel therapeutic approach for refractory PTC.

scholarly journals METTL14 promotes tumorigenesis by regulating lncRNA OIP5-AS1/miR-98/ADAMTS8 signaling in papillary thyroid cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaoping Zhang ◽  
Dan Li ◽  
Chengyou Jia ◽  
Haidong Cai ◽  
Zhongwei Lv ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Qrt Pcr ◽  
The Relationship

Abstract Background Papillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood. Methods Expression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC. Results Functional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways. Conclusions Collectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.

scholarly journals A miR-205-5p/GGCT/CD44 axis controls the progression of papillary thyroid cancer

2021 ◽  
Author(s):  
Han-ning Li ◽  
Hui-min Zhang ◽  
Xing-rui Li ◽  
Jun Wang ◽  
Tao Xu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Clinicopathological Characteristics ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Attractive Therapeutic Target ◽  
Epithelial Marker ◽  
Subcutaneous Xenograft

Abstract Background Papillary thyroid cancer (PTC) is the most common endocrine malignancy, despite marked achieves in recent decades, the mechanisms underlying the pathogenesis and progression for PTC are incomplete. Accumulating evidence shows that γ-glutamylcyclotransferase (GGCT), an enzyme participated in glutathione homeostasis that is elevated in multiple types of tumors, represents an attractive therapeutic target. Methods Bioinformatics, immunohistochemistry (IHC), qRT-PCR and western blot (WB) assays were used to determine the elevation of GGCT in PTC. The biological functions of GGCT were examined using CCK8, wound healing and transwell assays. Subcutaneous xenograft and tail vein pulmonary metastatic mouse models were constructed to determine the effect of GGCT on tumorigenicity and metastasis in vivo. The effect of miR-205-5p on GGCT and the relationship between these two molecules were examined by dual luciferase reporter assay, RNA-RNA pull down assay as well as the rescue experiments both in vitro and in vivo. The interaction between GGCT and CD44 was assessed by co-immunoprecipitation (Co-IP) and IHC assays. Results Our results showed that GGCT expression is upregulated in PTC, correlates with more aggressive clinicopathological characteristics and worse prognosis. GGCT knockdown inhibited the cell proliferation, migratory and invasion ability of PTC cells and reduced the expression of mesenchymal markers (N-cadherin, CD44, MMP-2 and MMP9) while increased epithelial marker (E-cadherin) in PTC cells. We confirmed binding of miR-205-5p on the 3’-UTR regions of GGCT and delivery of miR-205-5p reversed the pro-malignant capacity of GGCT both in vitro and in vivo. Lastly, we found GGCT interacted with and stabilized CD44 in PTC cells. Conclusions Our findings illustrate a novel signaling pathway, miR-205-5p/GGCT/CD44, that involves in the carcinogenesis and progression of PTC. Development of miR-205-mimics or GGCT inhibitors as potential therapeutics for PTC may have remarkable applications.

scholarly journals Antitumor effects of anlotinib in thyroid cancer

2019 ◽  
Vol 26 (1) ◽  
pp. 153-164 ◽  
Author(s):  
Xianhui Ruan ◽  
Xianle Shi ◽  
Qiman Dong ◽  
Yang Yu ◽  
Xiukun Hou ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Cancer Type ◽  
Papillary Thyroid ◽  
Antitumor Effects ◽  
Effective Therapeutic Strategy

There is no effective treatment for patients with poorly differentiated papillary thyroid cancer or anaplastic thyroid cancer (ATC). Anlotinib, a multi-kinase inhibitor, has already shown antitumor effects in various types of carcinoma in a phase I clinical trial. In this study, we aimed to better understand the effect and efficacy of anlotinib against thyroid carcinoma cells in vitro and in vivo. We found that anlotinib inhibits the cell viability of papillary thyroid cancer and ATC cell lines, likely due to abnormal spindle assembly, G2/M arrest, and activation of TP53 upon anlotinib treatment. Moreover, anlotinib suppresses the migration of thyroid cancer cells in vitro and the growth of xenograft thyroid tumors in mice. Our data demonstrate that anlotinib has significant anticancer activity in thyroid cancer, and potentially offers an effective therapeutic strategy for patients of advanced thyroid cancer type.

scholarly journals Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Junjie Chu ◽  
Li Tao ◽  
Teng Yao ◽  
Zizheng Chen ◽  
Xiaoxiao Lu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Promoting Effect

AbstractPapillary thyroid cancer (PTC) has a continuously increasing incidence and imposes a heavy medical burden to individuals and society due to its high proportion of lymph node metastasis and recurrence in recent years. Circular RNAs, a class of noncoding RNAs, participate in the progression of many cancers, but the role of circRNAs in PTC is still rarely reported. In this study, circRNA deep sequencing was performed to identify differentially expressed circRNAs in PTC. CircRUNX1 was selected for its high expression in PTC, and circRUNX1 silencing was directly associated with the week potential for migration, invasion and proliferation of PTC in vivo and in vitro. Fluorescence in situ hybridization (FISH) was further used to confirm the cytoplasmic localization of circRUNX1, indicating the possible function of circRUNX1 as a ceRNAs in PTC progression through miRNA binding. MiR-296-3p was then confirmed to be regulated by circRUNX1 and to target DDHD domain containing 2 (DDHD2) by luciferase reporter assays. The strong antitumor effect of miR-296-3p and the tumor-promoting effect of DDHD2 were further investigated in PTC, indicating that circRUNX1 modulates PTC progression through the miR-296-3p/DDHD2 pathway. Overall, circRUNX1 plays an oncogenic role in PTC and provides a potentially effective therapeutic strategy for PTC progression.

Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo

2014 ◽  
Vol 393 (1-2) ◽  
pp. 24-29 ◽  
Author(s):  
Sun Wook Cho ◽  
Ka Hee Yi ◽  
Sun Kyoung Han ◽  
Hyun Jin Sun ◽  
Ye An Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Therapeutic Potential ◽  
Papillary Thyroid

Investigating an orally available small-molecule inhibitor (vemurafenib) of BRAFV600E in a novel preclinical model of human papillary thyroid cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17014-e17014
Author(s):  
Mark Duquette ◽  
Peter M. Sadow ◽  
Carmen Priolo ◽  
Andrew Fischer ◽  
Richard Hodin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Therapeutic Efficacy ◽  
Thyroid Tissue ◽  
Genetic Alterations ◽  
Preclinical Model ◽  
Papillary Thyroid ◽  
Differentiation Markers ◽  
Therapeutic Model

e17014 Background: Patients with BRAFV600E-positive human papillary thyroid cancer (PTC) have poorer prognosis, higher rates of metastases and mortality, and resistance to radioiodine treatment. The goal of this study was to assess the therapeutic efficacy of vemurafenib (a new orally available BRAFV600E selective inhibitor) in a translational therapeutic model of BRAFV600E human nonmetastatic or metastatic PTC. Methods: We have established in vitro cultures of human primary PTC cells with or without heterozygous BRAFWT/V600E, primary normal thyroid (NT) cells, and used previously established human PTC cell lines with BRAFV600E. Immunocytochemistry was used to characterize markers of differentiation. Genotyping (over 500 genes analyzed) by mass spectrometry was performed to determine genetic alterations. Cell viability assays were performed upon different concentrations of vemurafenib: 0.01, 0.1, 1, 5, and 10 µM. Phosphorylation (p) of ERK1/2 (downstream BRAFV600E) was used to measure BRAFV600E activity. Results: We have isolated 8 independent batches of primary human non-metastatic or metastatic PTC cells from total thyroidectomy patients with PTC >1.1 cm, and 4 independent batches of primary NT cells from normal matched thyroid tissue specimens. 62.5% of the isolated batches of PTC cells were heterozygous BRAFWT/V600E and expressed epithelial markers and thyroid differentiation markers (e.g. PAX8, TSH-receptor). The NT cells showed no mutations. BRAFWT/V600E nonmetastatic PTC cells showed decreased viability (IC50: 5 µM) and pERK1/2 levels (IC90: 10 µM) when exposed to vemarufenib, with no toxic effects. PTC cells with BRAFWT, or NT cells showed no change in viability and pERK1/2 levels when exposed to vemarufenib. Importantly, BRAFWT/V600E metastatic PTC cells showed a partial suppression of viability and inhibition of pERK1/2 but only at a higher dose (10 µM) of vemurafenib. Conclusions: We have established the first translational therapeutic model of heterozygous BRAFWT/V600E-PTC. Testing of PTC samples for BRAFWT/V600E and testing in vitro will help predict therapeutic efficacy of Vemurafenib in patients with BRAFWT/V600E-PTC.

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