FK506-binding protein 5 promotes the progression of papillary thyroid carcinoma

Objective To detect the expression of FK506-binding protein 5 (FKBP5) in human papillary thyroid carcinoma (PTC) tissues, and explore its possible role in the progression of PTC. Methods FKBP5 expression levels were assessed in 115 PTC tissues and corresponding normal tissues by immunohistochemistry. We also examined the correlations between FKBP5 expression and clinicopathological factors and survival in 75 patients with PTC. The effects of FKBP5 on the proliferation and apoptosis of PTC cells were detected by colony-formation, MTT, and flow cytometry assays, respectively. We further investigated the effects of FKBP5 on tumor growth in mice. Results We revealed high expression levels of FKBP5 in human PTC tissues compared with normal tissues. Furthermore, high FKBP5 expression was associated with an increased incidence of intraglandular dissemination, and lower overall and progression-free survival. FKBP5 depletion remarkably suppressed the proliferation and induced apoptosis of PTC cells in vitro. FKBP5 further contributed to the growth of PTC tumors in mice. Conclusions The results of this study demonstrated the potential involvement of FKBP5 in the progression of PTC, and confirmed FKBP5 as a novel therapeutic target for PTC treatment.

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CircLDLR Promotes Papillary Thyroid Carcinoma Tumorigenicity by Regulating miR-637/LMO4 Axis

Disease Markers ◽

10.1155/2021/3977189 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yuan-ming Jiang ◽

Wei Liu ◽

Ling Jiang ◽

Hongbin Chang

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Migration And Invasion ◽

Circular Rnas ◽

Papillary Thyroid ◽

Induced Apoptosis

Background. Circular RNAs (circRNAs) have been reported to play important roles in the development and progression of papillary thyroid carcinoma (PTC). However, the function and molecular mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the tumorigenesis of PTC remain unknown. Results. In this study, circLDLR was found to be markedly upregulated in PTC tissues and cell lines, and knockdown of circLDLR inhibited PTC cell proliferation, migration, and invasion but induced apoptosis in vitro. Moreover, circLDLR acted as a sponge for miR-637, and miR-637 interference reversed the anticancer effects of circLDLR knockdown on PTC cells. LMO4 was verified to be a target of miR-637; LMO4 upregulation abolished miR-637 mediated inhibition of cell growth and metastasis in PTC. Additionally, circLDLR could indirectly modulate LMO4 via acting as a sponge of miR-637 in PTC cells. Besides that, xenograft analysis showed that circLDLR knockdown suppressed tumor growth in vivo via regulating LMO4 and miR-637. Conclusion. Taken together, these results demonstrated that circLDLR promoted PTC tumorigenesis through miR-637/LMO4 axis, which may provide a novel insight into the understanding of PTC tumorigenesis and be useful in developing potential targets for PTC treatment.

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PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma

BioMed Research International ◽

10.1155/2020/8954513 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Qin Chen ◽

Wen-Ying Yu ◽

Huan-Huan Zhang ◽

Song-Zhao Zhang ◽

Jie Fang ◽

...

Keyword(s):

Cell Proliferation ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Tumor Growth ◽

Papillary Thyroid ◽

Normal Tissues ◽

Cycle Arrest ◽

B Cell Leukemia

PBX3 (Pre-B-cell leukemia homeobox 3) had been considered to be a multifunctional oncogene which involved in tumor growth, invasion, and metastasis in leukemia and some solid tumors. However, the contribution of PBX3 to papillary thyroid carcinoma (PTC) remains unclear. In this study, we found that PBX3 expression was significantly upregulated in PTC tissues compared to adjacent normal tissues, and high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis of PTC patients. Overexpression of PBX3 in PTC cell lines promoted cell proliferation. Consistently, knockdown of PBX3 by shRNA induced cell cycle arrest at G0/G1 phase, and inhibited angiogenesis and tumor growth in vitro and in vivo. Furthermore, PBX3 promoted PTC cell proliferation and angiogenesis through activation of AT1R/VEGFR2 pathway while overexpression of AT1R and treatment with VEGFA reversed PBX3-shRNA-induced decreased phosphorylation of VEGFR2 and its downstream (ERK1/2, AKT and Src). It demonstrated that PBX3 could be used as a potential prognostic biomarker and therapeutic target for PTC.

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MiR-613 inhibits the proliferation, migration, and invasion of papillary thyroid carcinoma cells by directly targeting TAGLN2

Cancer Cell International ◽

10.1186/s12935-021-02083-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yonglian Huang ◽

Hengwei Zhang ◽

Lidong Wang ◽

Chenxi Liu ◽

Mingyue Guo ◽

...

Keyword(s):

Cell Proliferation ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Papillary Thyroid ◽

Mesenchymal Transition ◽

Normal Tissues

Abstract Background Papillary thyroid carcinoma (PTC), with a rapidly increasing incidence, is the most prevalent malignant cancer of the thyroid. However, its pathogenesis is unclear and its specific clinical indicators have not yet been identified. There is increasing evidence that microRNAs (miRNAs) play important roles in tumor occurrence and progression. Specifically, miR-613 participates in the regulation of tumor development in various cancers; however, its effects and mechanisms of action in PTC are still unclear. Therefore, in this study, we investigated the expression and function of miR-613 in PTC. Methods qRT-PCR was used to determine miR-613 expression in 107 pairs of PTC and adjacent-normal tissues as well as in PTC cell lines and to detect TAGLN2 mRNA expression in PTC tissues and adjacent normal tissues. Western blot analysis was performed to identify TAGLN2 and epithelial–mesenchymal transition (EMT) biomarkers. The effects of miR-613 on PTC progression were evaluated by performing MTS, wound-healing, and Transwell assays in vitro. Luciferase reporter assays were also performed to validate the target of miR-613. Results In PTC, miR-613 was significantly downregulated and its low expression level was associated with cervical lymph node metastasis. However, its overexpression significantly suppressed PTC cell proliferation, migration, and invasion and inhibited EMT. TAGLN2 was identified as a target of miR-613, which also significantly inhibited the expression of TAGLN2. Further, the restoration of TAGLN2 expression attenuated the inhibitory effects of miR-613 on PTC cell proliferation and metastasis. Conclusion Our findings demonstrated that miR-613 can suppress the progression of PTC cells by targeting TAGLN2, indicating that miR-613 plays the role of a tumor suppressor in PTC. Overall, these results suggest that the upregulation of miR-613 is a promising therapeutic strategy for PTC.

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Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302008000700018 ◽

2008 ◽

Vol 52 (7) ◽

pp. 1194-1200 ◽

Cited By ~ 2

Author(s):

Graciela A. de Cross ◽

Horacio Suarez ◽

Fabián Pitoia ◽

Daniel Moncet ◽

María Vanegas ◽

...

Keyword(s):

Lymph Node ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Metastatic Lymph Node ◽

Fatal Outcome ◽

Point Mutations ◽

Papillary Thyroid ◽

Signaling Mechanism ◽

Metastatic Lesions

A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.

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Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma Cells in Vitro and in Mouse Tumor Xenografts and Activates Autophagy and Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Signaling Pathway

Medical Science Monitor ◽

10.12659/msm.915387 ◽

2019 ◽

Vol 25 ◽

pp. 5054-5061 ◽

Cited By ~ 1

Author(s):

Chao Li ◽

Yuqiu Zhou ◽

Yongcong Cai ◽

Chunyan Shui ◽

Wei Liu ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Mammalian Target Of Rapamycin ◽

Akt Signaling ◽

Carcinoma Cells ◽

Mouse Tumor ◽

Papillary Thyroid ◽

Akt Signaling Pathway ◽

Tumor Xenografts

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Metformin reduces glycometabolism of papillary thyroid carcinoma in vitro and in vivo

Journal of Molecular Endocrinology ◽

10.1530/jme-16-0134 ◽

2017 ◽

Vol 58 (1) ◽

pp. 15-23 ◽

Cited By ~ 8

Author(s):

Chen-Tian Shen ◽

Wei-Jun Wei ◽

Zhong-Ling Qiu ◽

Hong-Jun Song ◽

Xin-Yun Zhang ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Xenograft Model ◽

Dependent Manner ◽

Papillary Thyroid ◽

Fdg Uptake ◽

Dose Dependent

More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0–10 mM for 48 h)-treated cells by 18F-FDG uptake assay and western blotting analysis, respectively. MicroPET/CT imaging was performed to detect 18F-FDG uptake in vivo. After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated. 18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro. Xenograft model of PTC using BCPAP cells was achieved successfully. MicroPET/CT imaging showed that in vivo 18F-FDG uptake decreased after treatment with metformin. Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformin-treated PTC xenograft model. In conclusion, metformin could reduce glucose metabolism of PTC in vitro and in vivo. Metformin, by targeting glycometabolism of cancer cells, could be a promising adjuvant therapy alternative in the treatment modality of advanced thyroid carcinoma.

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Rationales for the Use of Cancer Stem Cells Markers in the Staging of Papillary Thyroid Carcinoma

Journal of Oncology ◽

10.1155/2019/1659654 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Noah Abd-Alkader Mahmood ◽

Amer Talib Tawfeeq ◽

Israa Mhdi Al-Sudani ◽

Zaynab Saad Abd-Alghni

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Histopathological Examination ◽

Standard Procedure ◽

Tumor Stage ◽

Needle Aspiration ◽

Stem Cell Markers ◽

Papillary Thyroid ◽

Expression Levels ◽

Cancer Stem Cell Markers

Fine needle aspiration biopsy (FNAB) is a standard procedure for the detection of thyroid nodules malignancy, yet 10-25% of the sample diagnosed may go undetermined or suspicious. The utility of cancer stem cell markers (CSCM) as a differential diagnosis molecular marker in nodules of suspicious decision in FNAB was hypothesized. Papillary thyroid carcinoma (PTC) and thyroid fibroadenoma (TFA) samples were selected to test the hypothesis. The samples employed in this study were from patients who had thyroid hyperplasia and a suspicious or undetermined diagnosis by FNAB. The patient underwent a successful thyroidectomy at Al-Yarmouk Teaching Hospital in Baghdad between January 2015 and December 2017. All nodule samples underwent a systematic histopathological examination after resection. Tumors diagnosed as PTC and those diagnosed as fibroadenoma (TFA) were selected for this study. Collectively 39 PTC and 11 TFA nodules were included. Quantitative reverse transcriptase real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to determine levels of mRNA and proteins of CSCM ALDH1A1, CD44, ABCG2, and Oct3/4 in both types of tumors were used. This study revealed that the expression levels of CSCM were significantly increased in PTC tissues when compared to benign tissues and the positive correlation was found between the CSCM expression levels and tumor stage, size, and gender. In conclusion, for a more precise diagnosis, we suggest these markers be included in what is currently available to characterize malignancy from what is not in thyroid cancer, as well as for the staging process of PTC.

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