scholarly journals IRAK1, a Target of miR-146b, Reduces Cell Aggressiveness of Human Papillary Thyroid Carcinoma

2016 ◽  
Vol 101 (11) ◽  
pp. 4357-4366 ◽  
Author(s):  
Chen-Kai Chou ◽  
Shun-Yu Chi ◽  
Cai-Hua Huang ◽  
Fong-Fu Chou ◽  
Chao-Cheng Huang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Reporter Gene ◽  
Target Gene ◽  
Mrna Level ◽  
Advanced Tumor Stage ◽  
Papillary Thyroid ◽  
Extrathyroidal Invasion ◽  
Advanced Tumor ◽  
Reporter Gene Assays

Context: MicroRNA (miR)-146b is overexpressed in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal invasion, advanced tumor stage, and poor prognosis. However, the underlying mechanism of miR-146b in relation to its oncogenic behavior in PTC and its putative targets remain unknown. Objective: The purpose was to investigate IL-1 receptor-associated kinase 1 (IRAK1) as the potential miR-146b target gene and its involvement in PTC. Design: We used genome-wide microarray, computational analysis, and 3′ UTR reporter gene assays to identify IRAK1 as a miR-146b target gene. In vitro gain/loss-of-function experiments were further performed to determine the effects of IRAK1 on proliferation, colony formation, and wound-healing in PTC cancer cell lines. Expression levels of miR-146b and IRAK1 of 50 cases of PTC and its adjacent normal thyroid specimens were assessed via qRT-PCR. Results: Microarray expression profile revealed that the mRNA level of IRAK1 gene was down-regulated by miR-146b. The 3′ UTR of IRAK1 mRNA was found to be a molecular target of miR-146b posttranscriptional repression in BCPAP cells by reporter gene assays. MiR-146b promoted the migration and proliferation of PTC cells by down-regulating IRAK1 expression, whereas restoration of IRAK1 expression reversed this effect. In addition, the expression of IRAK1 mRNA was significantly lower in PTC clinical tissue samples than normal adjacent thyroid specimens and showed a strong inverse correlation with the expression of miR-146b in PTC specimens. Conclusion: Our results demonstrated that IRAK1 is a direct target of miR-146b and has functional roles to inhibit various aggressive PTC cell activities. In conjunction with current therapeutic regimens, targeting the miR-146b-IRAK1 axis may provide a potential approach for PTC management.

Identification of Differentially Expressed Genes Associated with Papillary Thyroid Carcinoma

2020 ◽  
Vol 23 (6) ◽  
pp. 546-553
Author(s):  
Hongyuan Cui ◽  
Mingwei Zhu ◽  
Junhua Zhang ◽  
Wenqin Li ◽  
Lihui Zou ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Mrna Level ◽  
Thyroid Tissue ◽  
Differentially Expressed ◽  
Thyroid Tumors ◽  
Papillary Thyroid

Objective: Next-generation sequencing (NGS) was performed to identify genes that were differentially expressed between normal thyroid tissue and papillary thyroid carcinoma (PTC). Materials & Methods: Six candidate genes were selected and further confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry in samples from 24 fresh thyroid tumors and adjacent normal tissues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to investigate signal transduction pathways of the differentially expressed genes. Results: In total, 1690 genes were differentially expressed between samples from patients with PTC and the adjacent normal tissue. Among these, SFRP4, ZNF90, and DCN were the top three upregulated genes, whereas KIRREL3, TRIM36, and GABBR2 were downregulated with the smallest p values. Several pathways were associated with the differentially expressed genes and involved in cellular proliferation, cell migration, and endocrine system tumor progression, which may contribute to the pathogenesis of PTC. Upregulation of SFRP4, ZNF90, and DCN at the mRNA level was further validated with RT-PCR, and DCN expression was further confirmed with immunostaining of PTC samples. Conclusion: These results provide new insights into the molecular mechanisms of PTC. Identification of differentially expressed genes should not only improve the tumor signature for thyroid tumors as a diagnostic biomarker but also reveal potential targets for thyroid tumor treatment.

scholarly journals CD74 expression and its therapeutic potential in thyroid carcinoma

2015 ◽  
Vol 22 (2) ◽  
pp. 179-190 ◽  
Author(s):  
Shih-Ping Cheng ◽  
Chien-Liang Liu ◽  
Ming-Jen Chen ◽  
Ming-Nan Chien ◽  
Ching-Hsiang Leung ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Therapeutic Potential ◽  
Thyroid Tissue ◽  
Anaplastic Thyroid Cancer ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Advanced Tumor Stage ◽  
Papillary Thyroid ◽  
Extrathyroidal Invasion ◽  
Advanced Tumor

CD74, the invariant chain of major histocompatibility complex class II, is also a receptor for macrophage migration inhibitory factor (MIF). CD74 and MIF have been associated with tumor progression and metastasis in hematologic and solid tumors. In this study, we found that 60 and 65% of papillary thyroid cancers were positive for CD74 and MIF immunohistochemical staining respectively. Anaplastic thyroid cancer was negative for MIF, but mostly positive for CD74 expression. Normal thyroid tissue and follicular adenomas were negative for CD74 expression. CD74 expression in papillary thyroid cancer was associated with larger tumor size (P=0.043), extrathyroidal invasion (P=0.021), advanced TNM stage (P=0.006), and higher MACIS score (P=0.026). No clinicopathological parameter was associated with MIF expression. Treatment with anti-CD74 antibody in thyroid cancer cells inhibited cell growth, colony formation, cell migration and invasion, and vascular endothelial growth factor secretion. In contrast, treatment with recombinant MIF induced an increase in cell invasion. Anti-CD74 treatment reduced AKT phosphorylation and stimulated AMPK activation. Our findings suggest that CD74 overexpression in thyroid cancer is associated with advanced tumor stage and may serve as a therapeutic target.

scholarly journals MiR-192-5p inhibits proliferation, migration, and invasion in papillary thyroid carcinoma cells by regulation of SH3RF3

2021 ◽  
Vol 41 (9) ◽  
Author(s):  
Songbo Fu ◽  
Chengxu Ma ◽  
Xulei Tang ◽  
Xiaoni Ma ◽  
Gaojing Jing ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Mrna Level ◽  
Ring Finger ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Papillary Thyroid ◽  
Anti Cancer

Abstract Background: The decreased level of miR-192-5p has been reported in several kinds of cancers, including bladder, colon, ovarian, and non-small cell lung cancer. However, the expression and function of miR-192-5p in papillary thyroid carcinoma/cancer (PTC) remains unknown. Objective: The present study aimed to explore the function and underlying mechanism of miR-192-5p in PTC development. Methods: PTC tissues and relative normal controls from PTC patients were collected. qRT-PCR analysis was performed to measure miR-192-5p and SH3RF3 mRNA level in PTC tissues and cell lines. CCK-8 method and FCM assay were used to test cell proliferation and apoptosis in TPC-1 cells, respectively. The abilities of cell migration and invasion were detected by wound healing and transwell assays, respectively. The protein expression was evaluated by Western blot. The interaction between miR-192-5p and Src homology 3 (SH3) domain containing ring finger 3 (SH3RF3) were confirmed by dual-luciferase reporter assay. Results: MiR-192-5p level was obviously decreased in PTC tissues and cell lines. Overexpression of miR-192-5p suppressed proliferation, migration, invasion, and EMT process, while induced apoptosis in TPC-1 cells. In addition, miR-192-5p negatively modulated SH3RF3 expression by binding to its 3′-untranslated region (3′UTR). Silencing SH3RF3 inhibited the migration, invasion, and EMT of TPC-1 cells. In the meantime, matrine, an alkaloid extracted from herb, exerted its anti-cancer effects in PTC cells dependent on increase in miR-192-5p expression and decrease in SH3RF3 expression. Conclusion: We firstly declared that miR-192-5p played a tumor suppressive role in PTC via targeting SH3RF3. Moreover, matrine exerted its anti-cancer effects in PTC via regulating miR-192-5p/SH3RF3 pathway.

Vascular invasion predicts advanced tumor characteristics in papillary thyroid carcinoma

2021 ◽  
Author(s):  
Jordan Reilly ◽  
Erfan Faridmoayer ◽  
Morta Lapkus ◽  
Jacquelyn Pastewski ◽  
Fionna Sun ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Vascular Invasion ◽  
Tumor Characteristics ◽  
Papillary Thyroid ◽  
Advanced Tumor

Tall cell variant: An aggressive form of papillary thyroid carcinoma

2000 ◽  
Vol 122 (3) ◽  
pp. 352-357 ◽  
Author(s):  
Stephen Prendiville ◽  
Kenneth D. Burman ◽  
Matthew D. Ringel ◽  
Barry M. Shmookler ◽  
Ziad E. Deeb ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Distant Metastases ◽  
Control Group ◽  
Papillary Thyroid ◽  
Tall Cell Variant ◽  
Extrathyroidal Invasion ◽  
Tall Cell ◽  
Cell Variant

Twenty-four cases of the tall cell variant (TCV), a subset of papillary thyroid carcinoma, were identified in a group of 624 patients with thyroid cancer. All pathology specimens were reviewed, and each patient's carcinoma was categorized according to characteristics on presentation, local recurrence, distant metastases, follow-up, and tumor-related mortality. The TCV group was compared with a historical control group (Mazzaferri and Jhiang: 1355 patients). The TCV group had a statistically higher percentage of stage 3 and 4 carcinoma, extrathyroidal invasion, and tumor size less than 1.5 cm than the control group. There was no statistical relationship between age greater than 50 years and stage in the TCV group. No relationship could be found between TCV histology and recurrence or mortality. These findings, combined with those of studies that link stage on presentation to poor outcomes, have led to our conclusion that TCV is an aggressive malignancy warranting appropriate treatment and close follow-up.

scholarly journals APOE is a Prognostic Biomarker and Correlates With Immune Infiltrates in Papillary Thyroid Carcinoma

2021 ◽  
Author(s):  
Xu Lin ◽  
Wen-Jing Zhang ◽  
Gang Xue ◽  
Jing-Fang Wu ◽  
Liu-ya Chao
Keyword(s):  
Lipid Metabolism ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Immune Cell ◽  
Mrna Level ◽  
Papillary Thyroid ◽  
Lipid Complex ◽  
Immune Biomarkers ◽  
Subunit Organization ◽  
Apoe Expression

Abstract Background: Recent research showed that abnormal lipid metabolism was associated with cancers. As one of the genes that can regulate the level of lipid metabolism, abnormal APOE expression was associated with carcinogenesis. However, the biological role of APOE in papillary thyroid carcinoma (PTC) remains to be determined.Methods: ONCOMINE, GEPIA, UALCAN, STRING, GeneMANIA, LinkedOmics, GSCALite, TISIDB, EPIC and TIMER were utilized to achieve comprehensively bioinformatics analysis of APOE in this study. And the immunohistochemical staining of APOE was used to verify the predicted results.Results: The mRNA level and protein level of APOE of PTC tissues were significantly elevated in TCGA cohort and Shanghai cohort. And APOE expression was positively correlated with the pathological stage and lymph node metastasis in PTC. PTC patients with low mRNA level of APOE were associated with a bad prognosis. The functions of APOE co-expressed genes were mainly enriched in adaptive immune response, protein-lipid complex subunit organization, actin cytoskeleton reorganization, cell chemotaxis, protein activation cascade and transcriptional misregulation in cancer. APOE level was significantly correlated with tumor-infiltrating cells (B cells, CD8+ T cells, neutrophils, and dendritic) and immune biomarkers in PTC.Conclusions: APOE is a potential independent biomarker for PTC and APOE expression is positively correlated with immune cell infiltration in PTC.

Tall Cell Variant: An Aggressive Form of Papillary Thyroid Carcinoma

2000 ◽  
Vol 122 (3) ◽  
pp. 352-357 ◽  
Author(s):  
Stephen Prendiville ◽  
Kenneth D. Burman ◽  
Matthew D. Ringel ◽  
Barry M. Shmookler ◽  
Ziad E. Deeb ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Distant Metastases ◽  
Control Group ◽  
Papillary Thyroid ◽  
Tall Cell Variant ◽  
Extrathyroidal Invasion ◽  
Tall Cell ◽  
Cell Variant

Twenty-four cases of the tall cell variant (TCV), a subset of papillary thyroid carcinoma, were identified in a group of 624 patients with thyroid cancer. All pathology specimens were reviewed, and each patient's carcinoma was categorized according to characteristics on presentation, local recurrence, distant metastases, follow-up, and tumor-related mortality. The TCV group was compared with a historical control group (Mazzaferri and Jhiang: 1355 patients). The TCV group had a statistically higher percentage of stage 3 and 4 carcinoma, extrathyroidal invasion, and tumor size less than 1.5 cm than the control group. There was no statistical relationship between age greater than 50 years and stage in the TCV group. No relationship could be found between TCV histology and recurrence or mortality. These findings, combined with those of studies that link stage on presentation to poor outcomes, have led to our conclusion that TCV is an aggressive malignancy warranting appropriate treatment and close follow-up.

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