METTL3-Induced miR-222-3p Upregulation Inhibits STK4 and Promotes the Malignant Behaviors of Thyroid Carcinoma Cells

2021 ◽  
Author(s):  
Shaojian Lin ◽  
Yue Zhu ◽  
Chengcheng Ji ◽  
Weiming Yu ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Nude Mice ◽  
Poor Prognosis ◽  
Carcinoma Cells ◽  
The Sun ◽  
Downstream Signaling ◽  
Functional Studies ◽  
Normal Tissues ◽  
Signaling Axis ◽  
Stress Kinase

Abstract Context Abnormally high expression of N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) has been implied to accompany thyroid carcinoma (TC) development. Objective This study aimed to explore the protumorigenic role and downstream signaling axis of METTL3 in TC. Methods This study was conducted at the Sun Yat-Sen Memorial Hospital Sun Yat-Sen University. METTL3 and miR-222-3p were overexpressed or downregulated in TC cells. Tumor and adjacent normal tissues were collected from 80 patients (19 men and 60 women, aged 30-70 years) with a pathological diagnosis of TC from January 2012 to January 2015. Cells were classified and subjected to different treatments. The expression of METTL3 was validated in TC tissues and cell lines. In functional studies, METTL3 and miR-222-3p were overexpressed or downregulated in TC cells to evaluate their effects on malignant behaviors, which were subsequently verified by xenografts in nude mice. Results The expression of METTL3 was elevated in TC, correlating with poor prognosis of TC patients. Heightened METTL3 expression accelerated malignant behaviors of TC cells. Mechanistically, METTL3 stimulated miR-222-3p expression by mediating the m6A modification of pri-miR-222-3p. miR-222-3p targeted and inversely regulated serine/threonine stress kinase 4 (STK4). Knockdown of METTL3 augmented STK4 expression by downregulating miR-222-3p, thereby suppressing the malignant behaviors of TC cells as well as tumor growth and lung metastasis in nude mice. Conclusion Silencing METTL3 suppresses miR-222-3p expression and thus stimulates STK4 expression, thereby repressing the malignancy and metastasis of TC.

scholarly journals DNAJB11 predicts a poor prognosis and is associated with immune infiltration in thyroid carcinoma: a bioinformatics analysis

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110537
Author(s):  
Rongxin Sun ◽  
Longyan Yang ◽  
Yan Wang ◽  
Yuanyuan Zhang ◽  
Jing Ke ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Bioinformatics Analysis ◽  
Enrichment Analysis ◽  
Mrna Levels ◽  
Normal Tissues ◽  
Go Enrichment ◽  
Low Levels ◽  
Go Enrichment Analysis

Objective To investigate the prognostic value of the co-chaperone protein DnaJ Heat Shock Protein Family (Hsp40) Member B11 (DNAJB11) in thyroid carcinoma (THCA). Methods This bioinformatics analysis study evaluated the prognostic value of DNAJB11 mRNA levels in THCA based on data from The Cancer Genome Atlas (TCGA). The levels of DNAJB11 mRNA in THCA and normal tissues were compared with Wilcoxon signed rank test. Kaplan–Meier survival curve analysis and Cox regression analysis were performed to evaluate the correlation between DNAJB11 mRNA levels and survival. Gene Ontology (GO) enrichment analysis was used to elucidate the functional enrichment difference. Results Data from the 502 patients with THCA from the TCGA database were analysed. DNAJB11 mRNA was downregulated in THCA tissues compared with normal tissues. Decreased levels of DNAJB11 mRNA were significantly correlated with T stage, N stage, pathological stage, histological type, extrathyroidal extension and BRAF gene status. The low levels of DNAJB11 mRNA were associated with a shorter progression-free interval. GO enrichment analysis showed that DNAJB11 was involved in immune-related biological processes. Conclusion Low levels of DNAJB11 mRNA were associated with poor prognosis in THCA.

HGF/SF downstream signaling in human hepatoblastoma and hepatocellular carcinoma cells

2004 ◽  
Vol 216 (03) ◽  
Author(s):  
S Grotegut ◽  
E Fasler-Kan ◽  
G Christofori ◽  
D von Schweinitz
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Hepatocellular Carcinoma Cells ◽  
Downstream Signaling

Interactions of Vascular Endothelial Growth Factor and p53 with miR-195 in Thyroid Carcinoma: Possible Therapeutic Targets in Aggressive Thyroid Cancers

2019 ◽  
Vol 19 (7) ◽  
pp. 561-570 ◽  
Author(s):  
Hamidreza Maroof ◽  
Soussan Irani ◽  
Armin Arianna ◽  
Jelena Vider ◽  
Vinod Gopalan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Cell Cycle Progression ◽  
P53 Protein ◽  
Carcinoma Cells ◽  
Vascular Endothelial ◽  
Papillary Thyroid ◽  
Cycle Progression ◽  
Thyroid Carcinomas ◽  
Endothelial Growth Factor

Background: The clinical pathological features, as well as the cellular mechanisms of miR-195, have not been investigated in thyroid carcinoma. Objective: The aim of this study is to identify the interactions of vascular endothelial growth factor (VEGF), p53 and miR-195 in thyroid carcinoma. The clinical and pathological features of miR-195 were also investigated. Methods: The expression levels of miR-195 were identified in 123 primary thyroid carcinomas, 40 lymph nodes with metastatic papillary thyroid carcinomas and seven non-neoplastic thyroid tissues (controls) as well as two thyroid carcinoma cell lines, B-CPAP (from metastasizing human papillary thyroid carcinoma) and MB-1 (from anaplastic thyroid carcinoma), by the real-time polymerase chain reaction. Using Western blot and immunofluorescence, the effects of exogenous miR-195 on VEGF-A and p53 protein expression levels were examined. Then, cell cycle and apoptosis assays were performed to evaluate the roles of miR-195 in cell cycle progression and apoptosis. Results: The expression of miR-195 was downregulated in majority of the papillary thyroid carcinoma tissue as well as in cells. Introduction of exogenous miR-195 resulted in downregulation of VEGF-A and upregulation of p53 protein expressions. Upregulation of miR-195 in thyroid carcinoma cells resulted in cell cycle arrest. Moreover, we demonstrated that miR-195 inhibits cell cycle progression by induction of apoptosis in the thyroid carcinoma cells. Conclusion: Our findings showed for the first time that miR-195 acts as a tumour suppressor and regulates cell cycle progression and apoptosis by targeting VEGF-A and p53 in thyroid carcinoma. The current study exhibited that miR-195 might represent a potential therapeutic target for patients with thyroid carcinomas having aggressive clinical behaviour.

scholarly journals Recruitment and Expansion of Tregs Cells in the Tumor Environment—How to Target Them?

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1850
Author(s):  
Justine Cinier ◽  
Margaux Hubert ◽  
Laurie Besson ◽  
Anthony Di Roio ◽  
Céline Rodriguez ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Major Function ◽  
Normal Tissues ◽  
Tumor Environment ◽  
Plastic Transformation

Regulatory T cells (Tregs) are present in a large majority of solid tumors and are mainly associated with a poor prognosis, as their major function is to inhibit the antitumor immune response contributing to immunosuppression. In this review, we will investigate the mechanisms involved in the recruitment, amplification and stability of Tregs in the tumor microenvironment (TME). We will also review the strategies currently developed to inhibit Tregs’ deleterious impact in the TME by either inhibiting their recruitment, blocking their expansion, favoring their plastic transformation into other CD4+ T-cell subsets, blocking their suppressive function or depleting them specifically in the TME to avoid severe deleterious effects associated with Treg neutralization/depletion in the periphery and normal tissues.

scholarly journals Characterization of LDD-2633 as a Novel RET Kinase Inhibitor with Anti-Tumor Effects in Thyroid Cancer

2021 ◽  
Vol 14 (1) ◽  
pp. 38
Author(s):  
Hyo Jeong Lee ◽  
Pyeonghwa Jeong ◽  
Yeongyu Moon ◽  
Jungil Choi ◽  
Jeong Doo Heo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitor ◽  
Point Mutations ◽  
Carcinoma Cells ◽  
Medullary Thyroid ◽  
Potent Inhibition ◽  
Kinase Inhibitory Activity

Rearranged during transfection (RET), a receptor tyrosine kinase, is activated by glial cell line-derived neurotrophic factor family ligands. Chromosomal rearrangement or point mutations in RET are observed in patients with papillary thyroid and medullary thyroid carcinomas. Oncogenic alteration of RET results in constitutive activation of RET activity. Therefore, inhibiting RET activity has become a target in thyroid cancer therapy. Here, the anti-tumor activity of a novel RET inhibitor was characterized in medullary thyroid carcinoma cells. The indirubin derivative LDD-2633 was tested for RET kinase inhibitory activity. In vitro, LDD-2633 showed potent inhibition of RET kinase activity, with an IC50 of 4.42 nM. The growth of TT thyroid carcinoma cells harboring an RET mutation was suppressed by LDD-2633 treatment via the proliferation suppression and the induction of apoptosis. The effects of LDD-2633 on the RET signaling pathway were examined; LDD-2633 inhibited the phosphorylation of the RET protein and the downstream molecules Shc and ERK1/2. Oral administration of 20 or 40 mg/kg of LDD-2633 induced dose-dependent suppression of TT cell xenograft tumor growth. The in vivo and in vitro experimental results supported the potential use of LDD-2633 as an anticancer drug for thyroid cancers.

scholarly journals LPAR5 Promotes Thyroid Carcinoma Cells Proliferation and Migration by Activating Class IA PI3K Catalytic Subunit p110β

2021 ◽  
Author(s):  
Wei‐Jun Zhao ◽  
Liu‐Lian Zhu ◽  
Wei‐Qiang Yang ◽  
Shuai‐Jun Xu ◽  
Jie Chen ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Carcinoma Cells ◽  
Catalytic Subunit ◽  
And Migration ◽  
Proliferation And Migration

Evaluation of E-Cadherin and β-Catenin Immunoreactivity for Determining Undifferentiated Cells in Anaplastic Thyroid Carcinoma

Pathobiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Risa Kanematsu ◽  
Mitsuyoshi Hirokawa ◽  
Aki Tanaka ◽  
Ayana Suzuki ◽  
Miyoko Higuchi ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Thyroid Carcinoma ◽  
Undifferentiated Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cells ◽  
Membrane Expression ◽  
Thyroid Carcinomas ◽  
Nuclear Expression ◽  
Thyroid Transcription Factor 1 ◽  
E Cadherin

<b><i>Introduction:</i></b> An immunohistochemical study has occasionally been performed to diagnose anaplastic thyroid carcinoma (ATC). However, antibodies to confirm the undifferentiated nature of ATC have not yet been evaluated. The aim of this study was to evaluate E-cadherin and β-catenin expressions in immunoreactivity to determine undifferentiated carcinoma cells in the diagnosis of ATC. <b><i>Methods:</i></b> We immunohistochemically examined 29 ATCs, 30 poorly differentiated thyroid carcinomas (PDTCs), 22 well-differentiated thyroid carcinomas (WDTCs), and 3 squamous cell carcinomas. Antibodies for thyroid transcription factor-1 (TTF-1), paired-box gene 8 (PAX8), β-catenin, and E-cadherin were used. <b><i>Results:</i></b> All WDTCs tested positive for TTF-1, PAX8, and E-cadherin. The positive rates of TTF-1, PAX8, and E-cadherin were 93.3, 93.3, and 100%, respectively, in PDTCs and 17.2, 51.7, and 10.3%, respectively, in ATCs. WDTC expressed the lateral cell membrane staining for β-catenin and E-cadherin, whereas PDTC showed circumferential cell membranous expression (fishnet pattern). β-catenin cell membrane expression in ATCs is lost or discontinuous. Carcinoma cells with β-catenin nuclear expression without cell membranous expression were scattered in 72.4% of ATCs but were not observed in the other carcinomas. <b><i>Conclusion:</i></b> We propose 3 immunohistochemical findings to determine undifferentiated carcinoma cells in the diagnosis of ATC: (1) β-catenin nuclear expression with no or reduced cell membranous expression, (2) the loss or discontinuous pattern of E-cadherin expression, and (3) the loss of PAX8 nuclear expression.

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