MiR-221 Regulates Suppressors of Cytokine Signaling 3-Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (SOCS3-JAK2/STAT3) Pathway and Affects Thyroid Cancer Cell Proliferation and Apoptosis

2022 ◽  
Vol 12 (5) ◽  
pp. 996-1001
Author(s):  
Neng Jiang ◽  
Shunfu Zhu ◽  
Jianjun Zhu
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Mrna Level ◽  
Cytokine Signaling ◽  
Thyroid Cancer Cell ◽  
Tumor Tissues ◽  
Proliferation And Apoptosis ◽  
Socs3 Expression ◽  
Thyroid Cancer Cells ◽  
Socs3 Mrna

Objective: Suppressors of cytokine signaling 3 (SOCS3) negatively regulates JAK-STAT signaling. Bioinformatics analysis showed a targeted relationship between miR-221 and SOCS3 mRNA 3′-UTR. This study investigated whether miR-221 regulates SOCS3 expression and affects thyroid cancer cells. Methods: Dual-luciferase reporter gene experiments verified the relationship between miR-221 and SOCS3. The tumor tissues and adjacent tissues of patients with thyroid cancer were collected to detect miR-221 and SOCS3 level. Thyroid cancer cell line KTC-1 cells were assigned into miR-NC group and miR-221 inhibitor group followed by analysis of SOCS3, p-JAK2, and p-STAT3 level by Real-time PCR, cell apoptosis and cell proliferation by flow cytometry and cell invasion by Transwell assay. Results: Compared with adjacent tissues, miR-221 level in tumor tissues was increased, and SCOS3 mRNA level was decreased. There was a targeted relationship between miR-221 and SOCS3 mRNA. MiR-221 level in KTC-1 and TPC-1 cells was increased, while SOCS3 mRNA level was decreased. MiR-221 inhibitor can significantly upregulate SOCS3 mRNA and protein in KTC-1 cells, reduce the expression of p-JAK2, p-STAT3 protein, increase cell apoptosis, and reduce cell proliferation and invasion. Conclusion: The increased miR-221 and decreased SOCS3 expression are related to thyroid cancer pathogenesis. MiR-221 can inhibit the expression of SOCS3, affect JAK-STAT signaling activity, and regulate the proliferation and apoptosis of thyroid cancer cells.

microRNA-221 (Mir-221) Influences Ovarian Cancer Cell Proliferation and Apoptosis Through Regulating Suppressors of Cytokine Signaling 3-Janus Kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) Pathway

2020 ◽  
Vol 10 (6) ◽  
pp. 889-894
Author(s):  
Jie Zhou ◽  
Yang Zhan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cytokine Signaling ◽  
Cancer Cell Proliferation ◽  
Skov3 Cells ◽  
Proliferation And Apoptosis ◽  
Socs3 Expression ◽  
Suppressors Of Cytokine Signaling ◽  
Socs3 Mrna

Suppressors of cytokine signaling 3 (SOCS3) regulates JAK-STAT signaling. Bioinformatics analysis showed a targeted relationship of Mir-221 with SOCS3 mRNA. Our study assessed whether Mir221 regulates SOCS3 expression and affects ovarian cancer cells. Ovarian cancer tissues were collected and compared with adjacent tissues to detect Mir-221 and SOCS3 expression. Ovarian cancer cell line SKOV3 cells were separated into miR-NC group and Mir-221 inhibitor group followed by analysis of Mir-221, SOCS3, p-JAK2, and p-STAT3 expression, cell apoptosis and proliferation. Compared with adjacent tissues, Mir-221 expression in tumor tissues was significantly elevated and SCOS3 mRNA level was decreased. There is a targeted relationship between miR-203 and SOCS3 mRNA. Compared with IOSE80 cells, ovarian cancer A2780 and SKOV3 cells presented significantly elevated Mir-221 level and decreased SOCS3 expression. Mir-221 inhibitor transfection significantly upregulated SOCS3, downregulated p-JAK2, p-STAT3 protein, promoted cell apoptosis and inhibited proliferation. The increased Mir-221 and decreased SOCS3 expression are related to the pathogenesis of ovarian cancer. Mir-221 downregulates SOCS3, affects the activity of JAK-STAT signaling, and regulates ovarian cancer cell proliferation and apoptosis.

scholarly journals Smad Ubiquitination Regulatory Factor 1 (Smurf1) Promotes Thyroid Cancer Cell Proliferation and Migration via Ubiquitin-Dependent Degradation of Kisspeptin-1

2018 ◽  
Vol 49 (5) ◽  
pp. 2047-2059 ◽  
Author(s):  
Chunyan Yan ◽  
Haiying Su ◽  
Xiyuan Song ◽  
Huiling Cao ◽  
Lingling Kong ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Thyroid Tumor ◽  
Thyroid Cancer Cell ◽  
Cancer Proliferation ◽  
Proliferation And Apoptosis ◽  
Proliferation And Metastasis ◽  
Thyroid Cancer Cells

Background/Aims: Thyroid cancer is the most common malignancy in human endocrine system. Smad ubiquitination regulatory factor 1 (Smurf1) is an E3 ubiquitin-protein ligase in ubiquitin-proteasome pathway (UPP) system. This study aimed to investigate the effects of Smurf1 on thyroid cancer proliferation and metastasis, as well as underlying potential mechanism. Methods: The expression levels of Smurf1 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of Smurf1 on thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were measured using trypan blue exclusion assay, two-chamber migration (invasion) assay, cell colony formation assay and Guava Nexin assay, respectively. The ubiquitination of kisspeptin-1 (KISS-1) was assessed by protein ubiquitination assay. Finally, the effects of KISS-1 overexpression on activity of nuclear factor-kappa B (NF-κB) signaling pathway, as well as thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were also detected, respectively. Results: Smurf1 was highly expressed in thyroid tumor tissues and thyroid cancer cells. Up-regulation of Smurf1 promoted the viability, migration, invasion and proliferation of thyroid cancer cells. Knockdown of Smurf1 had opposite effects. Moreover, smurf1 promoted the ubiquitination of KISS-1. Overexpression of KISS-1 inactivated NF-κB pathway, suppressed thyroid cancer cell viability, migration, invasion and proliferation, and induced cell apoptosis. Conclusion: Up-regulation of Smurf1 exerted important roles in thyroid cancer formation and development by promoting thyroid cancer proliferation and metastasis. The ubiquitin-dependent degradation of KISS-1 induced by Smurf1 and the activation of NF-κB signaling pathway might be involved in this process. Smurf1 could be an effective therapy target and biomarker for thyroid cancer treatment.

scholarly journals Adiponectin and leptin exert antagonizing effects on proliferation and motility of papillary thyroid cancer cell lines

2021 ◽  
Author(s):  
Ersilia Nigro ◽  
Francesca Maria Orlandella ◽  
Rita Polito ◽  
Raffaela Mariarosaria Mariniello ◽  
Maria Ludovica Monaco ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Papillary Thyroid Cancer ◽  
Cell Lines ◽  
Combined Treatment ◽  
Migration And Invasion ◽  
Thyroid Cancer Cell ◽  
Papillary Thyroid ◽  
Thyroid Cancer Cells

AbstractAdiponectin (Acrp30) and leptin, adipokines produced and secreted mainly by the adipose tissue, are involved in human carcinogenesis. Thyroid carcinomas are frequent endocrine cancers, and several evidences suggest that they are correlated with obesity. In this study, we first analyzed the expression levels and prognostic values of Acrp30, leptin, and their receptors in thyroid cancer cells. Then, we investigated the role of Acrp30 and leptin in proliferation, migration, and invasion. We found that Acrp30 treatment alone inhibits cell proliferation and cell viability in a time and dose-dependent manner; leptin alone does not influence thyroid cancer cells (BCPAP and K1) proliferation, but the combined treatment reverts Acrp30-induced effects on cell proliferation. Additionally, through wound healing and Matrigel Matrix invasion assays, we unveiled that Acrp30 inhibits thyroid cancer cell motility, while leptin induces the opposite effect. Importantly, in the combined treatment, Acrp30 and leptin exert antagonizing effects on papillary thyroid cancer cells’ migration and invasion in both BCPAP and K1 cell lines. Highlights of these studies suggest that Acrp30 and leptin could represent therapeutic targets and biomarkers for the management of thyroid cancer.

scholarly journals Circular RNA Circ_0067934 Attenuates Ferroptosis of Thyroid Cancer Cells by miR-545-3p/SLC7A11 Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui-Hui Wang ◽  
Jia-Ni Ma ◽  
Xiao-Rong Zhan
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Circular Rna ◽  
Negative Regulator ◽  
Cancer Cell Proliferation ◽  
Thyroid Cancer Cell ◽  
Critical Function ◽  
Thyroid Cancer Cells

Ferroptosis is an emerging programmed cell death distinguished from apoptosis and autophagy and plays essential roles in tumorigenesis. Thyroid cancer is a prevalent endocrine tumor, but the molecular mechanism of ferroptosis during thyroid cancer development remains unclear. Here, we identified the critical function of circular RNA circ_0067934 in repressing ferroptosis of thyroid cancer cells. Our data showed that the ferroptosis activator erastin decreased thyroid cancer cell viabilities, while the circ_0067934 shRNA further attenuated erastin-inhibited cell viabilities. The silencing of circ_0067934 enhanced the levels of ferroptosis-related markers, including Fe2+, iron, and ROS in the cells. The knockdown of circ_0067934 induced thyroid cancer cell apoptosis and repressed thyroid cancer cell proliferation in vitro and in vivo. Circ_0067934 upregulated the expression of the ferroptosis-negative regulator SLC7A11 by sponging and inhibiting miR-545-3p in thyroid cancer cells. The overexpression of SLC7A11 or the inhibitor of miR-545-3p reversed circ_0067934 silencing-regulated thyroid cancer cell proliferation. Therefore, we concluded that Circ_0067934 attenuated ferroptosis of thyroid cancer cells by miR-545-3p/SLC7A11 signaling. Circ_0067934 may serve as a potential therapeutic target by regulating ferroptosis for the treatment of thyroid cancer.

scholarly journals RET Regulates Human Medullary Thyroid Cancer Cell Proliferation through CDK5 and STAT3 Activation

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 860
Author(s):  
Chia-Herng Yue ◽  
Muhammet Oner ◽  
Chih-Yuan Chiu ◽  
Mei-Chih Chen ◽  
Chieh-Lin Teng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Medullary Thyroid Cancer ◽  
Receptor Protein ◽  
Cancer Cell Proliferation ◽  
Thyroid Cancer Cell ◽  
Cancer Proliferation ◽  
Medullary Thyroid

Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the parafollicular C-cells, which produces the hormone calcitonin. RET is a transmembrane receptor protein-tyrosine kinase, which is highly expressed in MTC. Our previous studies reported that cyclin-dependent kinase 5 (CDK5) plays a crucial role in cancer progression, including MTC. However, the role of CDK5 in GDNF-induced RET signaling in medullary thyroid cancer proliferation remains unknown. Here, we investigated RET activation and its biochemically interaction with CDK5 in GDNF-induced medullary thyroid cancer proliferation. Our results demonstrated that GDNF stimulated RET phosphorylation and thus subsequently resulted in CDK5 activation by its phosphorylation. Activated CDK5 further caused STAT3 activation by its specific phosphorylation at Ser727. Moreover, we also found that GDNF treatment enhanced ERK1/2 and EGR1 activity, which is involved in p35 activation. Interestingly, we identified for the first time that CDK5 physically interacted with RET protein in MTC. Overall, our results provide a new mechanism for medullary thyroid cancer cell proliferation, suggesting that targeting CDK5 may be a promising therapeutic candidate for human medullary thyroid cancer in the near future.

scholarly journals ZIC1 Is a Putative Tumor Suppressor in Thyroid Cancer by Modulating Major Signaling Pathways and Transcription Factor FOXO3a

2014 ◽  
Vol 99 (7) ◽  
pp. E1163-E1172 ◽  
Author(s):  
Wei Qiang ◽  
Yuan Zhao ◽  
Qi Yang ◽  
Wei Liu ◽  
Haixia Guan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Colony Formation ◽  
Promoter Hypermethylation ◽  
Migration And Invasion ◽  
Thyroid Cancer Cells

Context: ZIC1 has been reported to be overexpressed and plays an oncogenic role in some brain tumors, whereas it is inactivated by promoter hypermethylation and acts as a tumor suppressor in gastric and colorectal cancers. However, until now, its biological role in thyroid cancer remains totally unknown. Objectives: The aim of this study is to explore the biological functions and related molecular mechanism of ZIC1 in thyroid carcinogenesis. Setting and Design: Quantitative RT-PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes. Methylation-specific PCR was used to analyze promoter methylation of the ZIC1 gene. The functions of ectopic ZIC1 expression in thyroid cancer cells were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays. Results: ZIC1 was frequently down-regulated by promoter hypermethylation in both primary thyroid cancer tissues and thyroid cancer cell lines. Moreover, our data showed that ZIC1 hypermethylation was significantly associated with lymph node metastasis in patients with papillary thyroid cancer. Notably, restoration of ZIC1 expression in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest and apoptosis by blocking the activities of the phosphatidylinositol-3-kinase (PI3K)/Akt and RAS/RAF/MEK/ERK (MAPK) pathways, and enhancing FOXO3a transcriptional activity. Conclusions: Our data demonstrate that ZIC1 is frequently inactivated by promoter hypermethyaltion and functions as a tumor suppressor in thyroid cancer through modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a.

MicroRNA-16-5p Promoted Fibroblast-Like Synoviocyte Proliferation and Suppressed Apoptosis via Targeting Suppressor of Cytokine Signaling 6 (SOCS6) in Human Rheumatoid Arthritis

2021 ◽  
Vol 11 (9) ◽  
pp. 1744-1751
Author(s):  
Deqian Meng ◽  
Wenyou Pan ◽  
Ju Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Cytokine Signaling ◽  
Human Rheumatoid Arthritis ◽  
Reporter Assay ◽  
Functional Roles ◽  
Proliferation And Apoptosis ◽  
Fibroblast Like Synoviocytes

Accumulating evidence have indicated that MicroRNAs (miRNAs) are key regulators in human rheumatoid arthritis (RA). The aim of this study was to explore the functional roles of miR-16-5p in proliferation, inflammation, and apoptosis of fibroblast-like synoviocytes (FLS). The expression of miR-16-5p and SOCS6 in FLA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. Luciferase reporter assay was used to verify the direct target of miR-16-5p. Western blot analysis was performed to analysis the levels of SOCS6, Bcl-2, Bax and cleaved caspase 3. miR-16-5p expression was significantly upregulated while SOCS6 level was decreased in RA-FLS compared with normal FLS. In addition, luciferase reporter assay confirmed that SOCS6 was the target of miR-16-5p. Silencing of miR-16-5p inhibited cell proliferation, releases of TNF-α, IL-1β, IL-6 and IL-8, and induced the apoptosis. The effects of miR-16-5p silencing on RA-FLS were reversed by downregulation of SOCS6. In summary, knockdown of miR-16-5p could suppress cell proliferation and accelerate the apoptosis of RA-FLS through targeting SOCS6, which may provide a potential therapeutic target for patients with RA.

scholarly journals Protein Kinase A-Independent Inhibition of Proliferation and Induction of Apoptosis in Human Thyroid Cancer Cells by 8-Cl-Adenosine

2008 ◽  
Vol 93 (3) ◽  
pp. 1020-1029 ◽  
Author(s):  
Audrey J. Robinson-White ◽  
Hui-Pin Hsiao ◽  
Wolfgang W. Leitner ◽  
Elizabeth Greene ◽  
Andrew Bauer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cancer Cells ◽  
Human Thyroid ◽  
Inhibition Of Proliferation ◽  
Thyroid Cancer Cells ◽  
Kinase A

Abstract Purpose: Protein kinase A (PKA) affects cell proliferation in many cell types and is a potential target for cancer treatment. PKA activity is stimulated by cAMP and cAMP analogs. One such substance, 8-Cl-cAMP, and its metabolite 8-Cl-adenosine (8-Cl-ADO) are known inhibitors of cancer cell proliferation; however, their mechanism of action is controversial. We have investigated the antiproliferative effects of 8-Cl-cAMP and 8-CL-ADO on human thyroid cancer cells and determined PKA’s involvement. Experimental Design: We employed proliferation and apoptosis assays and PKA activity and cell cycle analysis to understand the effect of 8-Cl-ADO and 8-Cl-cAMP on human thyroid cancer and HeLa cell lines. Results: 8-Cl-ADO inhibited proliferation of all cells, an effect that lasted for at least 4 d. Proliferation was also inhibited by 8-Cl-cAMP, but this inhibition was reduced by 3-isobutyl-1-methylxanthine; both drugs stimulated apoptosis, and 3-isobutyl-1-methylxanthine drastically reduced 8-Cl-cAMP-induced cell death. 8-Cl-ADO induced cell accumulation in G1/S or G2/M cell cycle phases and differentially altered PKA activity and subunit levels. PKA stimulation or inhibition and adenosine receptor agonists or antagonists did not significantly affect proliferation. Conclusions: 8-Cl-ADO and 8-Cl-cAMP inhibit proliferation, induce cell cycle phase accumulation, and stimulate apoptosis in thyroid cancer cells. The effect of 8-Cl-cAMP is likely due to its metabolite 8-Cl-ADO, and PKA does not appear to have direct involvement in the inhibition of proliferation by 8-Cl-ADO. 8-Cl-ADO may be a useful therapeutic agent to be explored in aggressive thyroid cancer.

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