scholarly journals Fentanyl Exerts an Antitumor Effect on Papillary Thyroid Cancer by Regulating the miR-204/KLF5 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Dahao Lu ◽  
Lulu Jiang ◽  
Chen Dai ◽  
Keshi Yan ◽  
Ju Gao
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Tumor Development ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Antitumor Effects ◽  
Reporter Assays ◽  
Potential Antitumor

Fentanyl is a strong anesthetic analgesic drug that plays important roles in many types of cancers. However, the role of fentanyl in papillary thyroid cancer (PTC) tumor development remains ambiguous. In this study, we aimed to investigate the potential antitumor effects of fentanyl on PTC cell viability and invasion. Results of cell counting kit-8 and Transwell assays demonstrated that fentanyl treatment (5 ng/ml) reduced the viability and invasion of two PTC cells, TCP-1 and BCPAP. Our data subsequently showed that fentanyl induced antitumor effects by increasing miR-204 expressions. Furthermore, the results of luciferase reporter assays identified that miR-204 directly targets Krüppel-like transcription factor 5 (KLF5), which serves as tumor-promoting genes in many cancers. Further mechanistic analyses revealed that fentanyl performs its tumor-suppressive functions by regulating the miR-204/KLF5 axis in PTC cells. These results contribute to understanding the important role of fentanyl in treating PTC.

scholarly journals The NEAT1_2/miR-491 Axis Modulates Papillary Thyroid Cancer Invasion and Metastasis Through TGM2/NFκb/FN1 Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Sun ◽  
Yuan Qin ◽  
Zhihong Wang ◽  
Wenwu Dong ◽  
Liang He ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Nuclear Translocation ◽  
Transglutaminase 2 ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Invasion And Metastasis ◽  
Non Coding Rna ◽  
Reporter Assays ◽  
Functional Analyses

NEAT1 (nuclear paraspeckle assembly transcript 1) is an oncogenic long non-coding RNA (lncRNA) that facilitates tumorigenesis in multiple cancers. In papillary thyroid cancer (PTC), the molecular mechanism by which NEAT1 affects invasion and metastasis remains elusive. RNA sequencing was used to discover differentially expressed NEAT1_2 downstream genes. Protein and RNA expression analyses and immunohistochemistry detected the expression of NEAT1_2, Transglutaminase 2 (TGM2), and microRNA-491 (miR-491) among PTC and non-cancerous tissues. Transwell and wound healing assays, and a mouse model of lung metastasis were used for further functional analyses. Bioinformatics was performed to predict miRNAs binding to both NEAT1_2 and TGM2. Rescue experiments and dual-luciferase reporter assays were performed. In PTC tissues, NEAT1_2 expression was markedly increased and regulated TGM2 expression. TGM2 was overexpressed in PTC, correlating positively with exthyroidal extension and lymph node metastasis. TGM2 knockdown significantly inhibited invasion and metastasis. NEAT1_2 sponged miR-491, acting as a competing endogenous RNA to regulate TGM2 expression. Fibronectin 1 (FN1) was predicted as a TGM2 target. TGM2 could transcriptionally activate FN1 by promoting nuclear factor kappa B (NFκb) p65 nuclear translocation, ultimately promoting PTC invasion/metastasis. These findings identify that NEAT1_2 sponges miR-491 to regulate TGM2 expression. TGM2 activates FN1 via NFκb to promote PTC invasion and metastasis.

scholarly journals Circular RNA circ-NCOR2 accelerates papillary thyroid cancer progression by sponging miR-516a-5p to upregulate metastasis-associated protein 2 expression

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052093465
Author(s):  
Sha Luan ◽  
Peng Fu ◽  
Xinyu Wang ◽  
Yue Gao ◽  
Ke Shi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Luciferase Reporter Gene ◽  
Vital Functions

Objective Papillary thyroid cancer (PTC) is one of the most prevalent endocrine malignancies and the fifth most common cancer in women. Circular RNAs (circRNAs) have been shown to play vital functions in cancers, but few studies have focused on the functions and mechanism of dysregulated circRNAs in PTC. Methods Quantitative reverse transcription PCR was used to measure circ-NCOR2 levels in PTC tissues and cell lines. The functions of circ-NCOR2 in PTC were examined by analysis using the cell counting kit-8, clone forming, flow cytometry, and Transwell experiments. Bioinformatic analysis and dual luciferase reporter gene testing were used to identify the mechanisms of circ-NCOR2. Results Circ-NCOR2 overexpression was observed in PTC tissues and cells. Silenced or overexpressed expression of circ-NCOR2 strikingly attenuated or facilitated, respectively, the growth, migration, and invasion of PTC cells. Mechanistically, miR-615a-5p was identified as the target of circ-NCOR2. Moreover, circ-NCOR2 enhanced the expression of metastasis-associated protein 2 (MTA2) by sponging miR-615a-5p, thereby facilitating PTC cell progression. Conclusions Taken together, our findings reveal a novel circ-NCOR2/miR-615a-5p/MTA2 axis in PTC, which could become a potential therapeutic target for this disease.

scholarly journals MicroRNA-96-3p promotes metastasis of papillary thyroid cancer through targeting SDHB

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xupeng Zhao ◽  
Yingjie Li ◽  
Yong Zhou
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Metastasis ◽  
Papillary Thyroid ◽  
Migration Ability ◽  
Non Coding Rna ◽  
Reporter Assays ◽  
Direct Targeting

Abstract Background MicroRNA (MiRNA) is a small non-coding RNA which is implicated in a cohort of biological function in cancer, including proliferation, metastasis, apoptosis and invasion. MiR-96 has been reported to be involved in many cancers, including papillary thyroid cancer. However, the role of miR-96-3p in papillary thyroid cancer metastasis is still unclear. Methods qRT-PCR is used to detect the level of miR-96-3p and mRNA of SDHB in PTC tissues and cell lines. Western blot assays are used to verify the protein expression of SDHB. The transwell assays are performed to identify the migration ability of PTC cell lines. Moreover, dual-luciferase 3′-UTR reporter assays are chosen to illuminate the direct target of miR-96-3p. Results The relative miR-96-3p upregulate in PTC tissues and three PTC cell lines (B-CPAP, K-1 and TPC-1 cells) while the relative SDHB is opposite. Our results revealed that the miR-96-3p promotes metastasis and invasion in PTC cell lines (K-1 and TPC-1 cells) by direct targeting SDHB and influence the downstream protein AKT. Conclusions Taken together, the miR-96-3p is involved in PTC metastasis and invasion by direct targeting SDHB and the downstream molecule AKT and mTOR.

scholarly journals Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luyao Wu ◽  
Yu Ding ◽  
Houchao Tong ◽  
Xi Zhuang ◽  
Jingsheng Cai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Noncoding Rna ◽  
Animal Experiments ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Loss Of Function ◽  
Functional Roles

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. Methods The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). Results Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. Conclusions This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.

scholarly journals METTL14 promotes tumorigenesis by regulating lncRNA OIP5-AS1/miR-98/ADAMTS8 signaling in papillary thyroid cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaoping Zhang ◽  
Dan Li ◽  
Chengyou Jia ◽  
Haidong Cai ◽  
Zhongwei Lv ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Qrt Pcr ◽  
The Relationship

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.

The Role of Different Molecular Markers in Papillary Thyroid Cancer Patients with Acromegaly

2018 ◽  
Vol 127 (07) ◽  
pp. 437-444 ◽  
Author(s):  
Fatma Ela Keskin ◽  
Hande Mefkure Ozkaya ◽  
Sina Ferahman ◽  
Ozlem Haliloglu ◽  
Adem Karatas ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Ex Vivo ◽  
Papillary Thyroid ◽  
Cerrahpasa Medical Faculty ◽  
Protein Expressions ◽  
Galectin 3 ◽  
Benign Nodules ◽  
Igf1 Expression

Abstract Purpose Prevalence of papillary thyroid cancer (PTC) is increased in patients with acromegaly. We aimed to determine the protein expression of BRAF, RAS, RET, insulin like growth factor 1(IGF1), Galectine 3, CD56 in patients with PTC related acromegaly and to compare the extensity of these expressions with normal PTC patients and benign thyroid nodules. Methods We studied 313 patients with acromegaly followed in Cerrahpasa Medical Faculty, Endocrinology and Metabolism Clinic between 1998 and 2015. On the basis of availability of pathological specimen of thyroid tissues, thyroid samples of 13 patients from 19 with acromegaly related PTC (APTC), 20 normal PTC and 20 patients with multinodulary goiter (MNG) were histopathologically evaluated. Protein expressions were determined via immunohistochemical staining in ex-vivo tumor samples and benign nodules. Results The incidence of PTC in acromegaly patients were 6% (n=19). Among patients with PTC, APTC and MNG, all the immunohistochemical protein expressions we have studied were higher in papillary thyroid cancer groups (p<0.01, for all). Between PTC group without acromegaly and APTC, galectin 3 and IGF1 expression was significantly higher in acromegalic patients (p<0.01 for all) while RAS was predominantly higher in PTC patients without acromegaly (p<0.01). Conclusion BRAF expression was not higher in PTC with acromegaly patients compared to PTC patients without acromegaly. Galectine 3 and IGF1 were expressed more intensively in APTC. These positive protein expressions may have more influence on determining malign nodules among acromegaly patients.

scholarly journals MicroRNA-384 Inhibits the Progression of Papillary Thyroid Cancer by Targeting PRKACB

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Yongxia Wang ◽  
Beixi Wang ◽  
Hong Zhou ◽  
Xiangnan Zhang ◽  
Xinlai Qian ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Target Gene ◽  
Underlying Mechanism ◽  
Soft Agar ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Soft Agar Assay ◽  
Spearman’S Correlation ◽  
Dual Luciferase Reporter Assay

Background. Growing evidence shows that dysregulation of miRNAs plays a significant role in papillary thyroid cancer (PTC) tumorigenesis and development. The abnormal expression of miR-384 has been acknowledged in the proliferation or metastasis of some cancers. However, the function and the underlying mechanism of miR-384 in PTC progression remain largely unknown. Methods. Real-time PCR was conducted to detect miR-384 expression in 58 cases of PTC and their adjacent noncancerous tissues. MTT, soft agar assay Transwell assay, and wound-healing assay were carried out to explore the biological function of miR-384 in PTC cell lines of BCPAP and K1. Bioinformatics analysis, dual-luciferase reporter assay, western blot, and functional complementation analysis were conducted to explore the target gene of miR-384. Moreover, Spearman’s correlation analysis was conducted to reveal the correlation between miR-384 and PRKACB mRNA in PTC. Results. The expression of miR-384 decreased obviously in PTC, especially in the tumors with lymph node metastasis or larger tumor size. The ectopic upregulation of miR-384 significantly suppressed PTC progression, and the inhibition of miR-384 had the opposite effects. Moreover, PRKACB gene was confirmed as the target of miR-384. Conclusion. The study suggests that miR-384 serves as a tumor suppressor in PTC progression by directly targeting the 3′-UTR of PRKACB gene.

scholarly journals The Role of miRNA in Papillary Thyroid Cancer in the Context of miRNA Let-7 Family

2016 ◽  
Vol 17 (6) ◽  
pp. 909 ◽  
Author(s):  
Ewelina Perdas ◽  
Robert Stawski ◽  
Dariusz Nowak ◽  
Maria Zubrzycka
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Papillary Thyroid
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