MiR-3121-3p promotes tumor invasion and metastasis by suppressing Rap1GAP in papillary thyroid cancer in vitro

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.

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Tamoxifen inhibits growth, migration, and invasion of human follicular and papillary thyroid cancer cells in vitro and in vivo.

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.80.1.7829632 ◽

1995 ◽

Vol 80 (1) ◽

pp. 308-313

Author(s):

T Hoelting ◽

A E Siperstein ◽

Q Y Duh ◽

O H Clark

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Papillary Thyroid Cancer ◽

Migration And Invasion ◽

Papillary Thyroid ◽

Thyroid Cancer Cells

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Dual inhibition of BRAF and MEK increases expression of sodium iodide symporter in patient-derived papillary thyroid cancer cells in vitro

Surgery ◽

10.1016/j.surg.2019.04.076 ◽

2020 ◽

Vol 167 (1) ◽

pp. 56-63 ◽

Cited By ~ 2

Author(s):

Timothy M. Ullmann ◽

Heng Liang ◽

Maureen D. Moore ◽

Isra Al-Jamed ◽

Katherine D. Gray ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Papillary Thyroid Cancer ◽

Sodium Iodide ◽

Papillary Thyroid ◽

Sodium Iodide Symporter ◽

Dual Inhibition ◽

Thyroid Cancer Cells

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Tamoxifen inhibits growth, migration, and invasion of human follicular and papillary thyroid cancer cells in vitro and in vivo

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.80.1.308 ◽

1995 ◽

Vol 80 (1) ◽

pp. 308-313 ◽

Cited By ~ 12

Author(s):

T. Hoelting

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Papillary Thyroid Cancer ◽

Migration And Invasion ◽

Papillary Thyroid ◽

Thyroid Cancer Cells

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Desensitization of cyclic adenosine 3,5′-monophosphate response to thyrotropin in normal and primary or metastatic papillary thyroid cancer cells in vitro

Surgery ◽

10.1016/s0039-6060(96)80035-3 ◽

1996 ◽

Vol 120 (6) ◽

pp. 926-933 ◽

Cited By ~ 3

Author(s):

Serdar Tezelman ◽

Allan E. Siperstein ◽

Quan-Yang Duh ◽

Mariwil G. Wong ◽

Orlo H. Clark

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Papillary Thyroid Cancer ◽

Papillary Thyroid ◽

Thyroid Cancer Cells

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Downregulation of TSPAN13 by miR-369-3p inhibits cell proliferation in papillary thyroid cancer (PTC)

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2018.2865 ◽

2018 ◽

Cited By ~ 5

Author(s):

Peng Li ◽

Mingqiang Dong ◽

Zhigang Wang

Keyword(s):

Cell Proliferation ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Expression Profiles ◽

Surface Proteins ◽

The Cancer Genome Atlas ◽

Luciferase Reporter ◽

Papillary Thyroid ◽

Small Interfering Rnas

Previous studies demonstrated dysregulation of different microRNAs in thyroid cancer. Tetraspanins (TSPANs) are cell surface proteins with critical roles in many cellular processes, and implications in tumor development. Here we investigated the role of miR-369-3p in papillary thyroid cancer (PTC) and its association with TSPAN13. miR-369-3p and the TSPAN13 gene expression profiles of 513 thyroid cancer and 59 normal thyroid tissues were downloaded from the Cancer Genome Atlas database. Thyroid cancer tissues were classified according to the histological type, grouped based on low and high median miR-369-3p and TSPAN13 expression, and analyzed in relation to overall survival (OS) of patients. Human PTC cell lines (TPC-1 and GLAG-66) and human embryonic kidney 293T (HEK293T) cells were used for in vitro analysis. Transfection experiments were performed with synthetic miRNA mimics for miR-369-3p and small interfering RNAs for TSPAN13. Relative expression of miR-369-3p and TSPAN13 mRNA was determined by RT-qPCR. Protein levels of TSPAN13 were determined by western blotting. Cell proliferation (CCK-8 assay), colony formation, and apoptosis (flow cytometry) were analyzed in transfected cells. Binding sites of miR-369-3p in TSPAN13 mRNA were determined by bioinformatics analysis and dual luciferase reporter assay. miR-369-3p was downregulated and TSPAN13 upregulated in PTC, follicular thyroid cancer, and tall cell variant tissues. Both low expression of miR-369-3p and high expression of TSPAN13 were associated with shorter OS in thyroid cancer patients. Overexpression of miR-369-3p significantly suppressed proliferation and promoted apoptosis in PTC cells. TSPAN13 was a direct target of miR-369-3p, and silencing of TSPAN13 phenocopied the effect of miR-369-3p mimics in PTC cells. Overall, the downregulation of miR-369-3p and consequent upregulation of its target TSPAN13 appear to be involved in pathophysiology of PTC.

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Organoid Cultures Derived From Patients With Papillary Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab020 ◽

2021 ◽

Author(s):

Dong Chen ◽

Yawen Tan ◽

Zhichao Li ◽

Wujiao Li ◽

Lei Yu ◽

...

Keyword(s):

Cell Proliferation ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Treatment Options ◽

Estrogen Receptor Α ◽

Patient Specific ◽

Preclinical Model ◽

Papillary Thyroid ◽

Promote Cell Proliferation

Abstract Context Papillary thyroid cancer (PTC) has been one of the most frequent endocrine malignancies around the world. Although most PTC patients have a favorable prognosis, a subgroup of patients die, especially when disease recurrence occurs. There is a pressing need for clinically relevant preclinical thyroid cancer models for personalized therapy because of the lack of in vitro models that faithfully represent the biology of the parental tumors. Objective To understand thyroid cancer and translate this knowledge to clinical applications, patient-derived PTC organoids as a promising new preclinical model were established. Methods Surgically resected PTC primary tissues were dissociated and processed for organoid derivation. Tumor organoids were subsequently subjected to histological characterization, DNA sequencing, drug screen, and cell proliferation assay, respectively. Results We describe a 3-dimensional culture system for the long-term expansion of patient-derived PTC organoid lines. Notably, PTC organoids preserve the histopathological profiles and genomic heterogeneity of the originating tumors. Drug sensitivity assays of PTC organoids demonstrate patient-specific drug responses, and large correlations with the respective mutational profiles. Estradiol was shown to promote cell proliferation of PTC organoids in the presence of estrogen receptor α (ERα), regardless of the expression of ERβ and G protein–coupled ER. Conclusion These data suggest that these newly developed PTC-derived organoids may be an excellent preclinical model for studying clinical response to anticancer drugs in a personalized way, as well as provide a potential strategy to develop prevention and treatment options for thyroid cancer with ERα-specific antagonists.

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

10.21203/rs.3.rs-965023/v1 ◽

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.

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