MEK Inhibitor PD0325901 Significantly Reduces the Growth of Papillary Thyroid Carcinoma Cells In vitro and In vivo

Background. Circular RNAs (circRNAs) have been reported to play important roles in the development and progression of papillary thyroid carcinoma (PTC). However, the function and molecular mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the tumorigenesis of PTC remain unknown. Results. In this study, circLDLR was found to be markedly upregulated in PTC tissues and cell lines, and knockdown of circLDLR inhibited PTC cell proliferation, migration, and invasion but induced apoptosis in vitro. Moreover, circLDLR acted as a sponge for miR-637, and miR-637 interference reversed the anticancer effects of circLDLR knockdown on PTC cells. LMO4 was verified to be a target of miR-637; LMO4 upregulation abolished miR-637 mediated inhibition of cell growth and metastasis in PTC. Additionally, circLDLR could indirectly modulate LMO4 via acting as a sponge of miR-637 in PTC cells. Besides that, xenograft analysis showed that circLDLR knockdown suppressed tumor growth in vivo via regulating LMO4 and miR-637. Conclusion. Taken together, these results demonstrated that circLDLR promoted PTC tumorigenesis through miR-637/LMO4 axis, which may provide a novel insight into the understanding of PTC tumorigenesis and be useful in developing potential targets for PTC treatment.

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Metformin reduces glycometabolism of papillary thyroid carcinoma in vitro and in vivo

Journal of Molecular Endocrinology ◽

10.1530/jme-16-0134 ◽

2017 ◽

Vol 58 (1) ◽

pp. 15-23 ◽

Cited By ~ 8

Author(s):

Chen-Tian Shen ◽

Wei-Jun Wei ◽

Zhong-Ling Qiu ◽

Hong-Jun Song ◽

Xin-Yun Zhang ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Xenograft Model ◽

Dependent Manner ◽

Papillary Thyroid ◽

Fdg Uptake ◽

Dose Dependent

More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0–10 mM for 48 h)-treated cells by 18F-FDG uptake assay and western blotting analysis, respectively. MicroPET/CT imaging was performed to detect 18F-FDG uptake in vivo. After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated. 18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro. Xenograft model of PTC using BCPAP cells was achieved successfully. MicroPET/CT imaging showed that in vivo 18F-FDG uptake decreased after treatment with metformin. Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformin-treated PTC xenograft model. In conclusion, metformin could reduce glucose metabolism of PTC in vitro and in vivo. Metformin, by targeting glycometabolism of cancer cells, could be a promising adjuvant therapy alternative in the treatment modality of advanced thyroid carcinoma.

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An aqueous extract of Prunella vulgaris L. inhibits the growth of papillary thyroid carcinoma by inducing autophagy in vivo and in vitro

Phytotherapy Research ◽

10.1002/ptr.7015 ◽

2021 ◽

Author(s):

Jia Song ◽

Zhengbao Zhang ◽

Youkun Hu ◽

Ziyin Li ◽

Yu Wan ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Aqueous Extract ◽

Papillary Thyroid ◽

Prunella Vulgaris

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miR-30b-5p inhibits proliferation, invasion, and migration of papillary thyroid cancer by targeting GALNT7 via the EGFR/PI3K/AKT pathway

Cancer Cell International ◽

10.1186/s12935-021-02323-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ye Wang ◽

Congjun Wang ◽

Zhao Fu ◽

Siwen Zhang ◽

Junqiang Chen

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Kinase Inhibitors ◽

Akt Pathway ◽

Papillary Thyroid ◽

Invasion And Migration ◽

Qrt Pcr ◽

And Migration

Abstract Background Papillary thyroid carcinoma (PTC) is a common endocrine tumor. Increasing evidence has shown that microRNA dysfunction is involved in the occurrence and development of cancer. The expression of MicroRNA-30b-5p (miR-30b-5p) was down-regulated in PTC; however, its role in the development of PTC is not clear. Hence, this study aimed to explore the role and mechanism of miR-30b-5p in the occurrence and development of PTC. Methods The qRT-PCR assay was used to detect the expression of miR-30b-5p in 60 cases of papillary thyroid carcinoma along with their matched non-cancerous tissues. This study explored the biological function of miR-30b-5p by the functional gain and loss experiments in vitro and vivo. The direct target gene of miR-30b-5p and its signaling pathway was identified through bioinformatics analysis, qRT-PCR, western blot, rescue experiments, and double luciferase 3'-UTR report analysis. Results This study demonstrated that the low expression of miR-30b-5p is related to poor clinicopathological features. Functionally, the overexpression of miR-30b-5p inhibited the proliferation, invasion, and migration of PTC cells. Bioinformatics and luciferase analysis showed that GALNT7 is the direct and functional target of miR-30b-5p. Moreover, miR-30b-5p inhibited the proliferation of PTC in vivo by inhibiting the expression of GALNT7. The studies on the mechanism have shown that GALNT7 promotes cell proliferation and invasion by activating EGFR/PI3K/AKT kinase pathway, which can be attenuated by the kinase inhibitors. Conclusions Overall, miR-30b-5p inhibited the progression of papillary thyroid carcinoma by targeting GALNT7 and inhibiting the EGFR/PI3K/AKT pathway.

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Down-regulated HSDL2 expression suppresses cell proliferation and promotes apoptosis in papillary thyroid carcinoma

Bioscience Reports ◽

10.1042/bsr20190425 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 3

Author(s):

Jing Zeng ◽

Xiao Ma ◽

Jinjing Wang ◽

Ran Liu ◽

Yun Shao ◽

...

Keyword(s):

Cell Proliferation ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Target Genes ◽

Mrna Level ◽

Papillary Thyroid ◽

Bioinformatics Analyses ◽

In Vivo Experiments

Abstract Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Hydroxysteroid dehydrogenase like 2 (HSDL2) can regulate lipid metabolism and take part in cell proliferation. The purpose of the present study was to explore functional role of HSDL2 gene in PTC. The expression of HSDL2 protein in PTC tissues was estimated using immunohistochemistry analysis (IHC). HSDL2 mRNA level was detected through quantitative real-time polymerase chain reaction (qRT-PCR). Effects of HSDL2 gene on cell proliferation and apoptosis were assessed using the shRNA method for both in vitro and in vivo experiments. Potential target genes of HSDL2 were determined via bioinformatics analyses and Western blotting. HSDL2 was up-regulated in PTC tissues and cell lines compared with the controls (all P<0.05). Inhibiting HSDL expression could suppress PTC cell proliferation and cycle, and promote apoptosis in vitro. In vivo, the knockdown of HSDL2 gene could significantly suppress tumor growth (all P<0.05). Furthermore, AKT3, NFATc2 and PPP3CA genes might be potential targets of HSDL2 in PTC. HSDL2 expression was increased in PTC tissues and cells, which could promote tumor progression in vitro and in vivo.

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BRAFV600E and RET/PTC Promote Proliferation and Migration of Papillary Thyroid Carcinoma Cells In Vitro by Regulating Nuclear Factor-κB

Medical Science Monitor ◽

10.12659/msm.904928 ◽

2017 ◽

Vol 23 ◽

pp. 5321-5329 ◽

Cited By ~ 7

Author(s):

Dehua Zhou ◽

Zhou Li ◽

Xuefeng Bai

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Nuclear Factor Κb ◽

Carcinoma Cells ◽

Nuclear Factor ◽

Papillary Thyroid ◽

And Migration ◽

Proliferation And Migration

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Circ_0039411 promotes papillary thyroid carcinoma development through mediating the miR-423-5p/SOX4 signaling

The International Journal of Biological Markers ◽

10.1177/17246008211043128 ◽

2021 ◽

pp. 172460082110431

Author(s):

Xiaohui Wen ◽

Jingyan Du ◽

Xun Wang

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Colony Formation ◽

Quantitative Polymerase Chain Reaction ◽

Carcinoma Cells ◽

Luciferase Reporter ◽

Papillary Thyroid ◽

Western Blot Assay ◽

Mediated Effects

Background Papillary thyroid carcinoma is the most frequent histological subtype of thyroid cancer with a high incidence. We aimed to explore the function of circular RNA_0039411 (circ_0039411) and its associated mechanism in papillary thyroid carcinoma progression. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine the expression of RNA and protein, respectively. The colony formation ability, migration, invasion, and apoptosis were analyzed by colony formation assay, transwell migration assay, transwell invasion assay, and flow cytometry. Cell glycolytic metabolism was analyzed using fluorescence-based glucose assay kit and fluorescence-based lactate assay kit. Dual-luciferase reporter assay and RNA-Pull-Down Assay were performed to validate the binding between microRNA-423-5p (miR-423-5p) and circ_0039411 or SRY-box transcription factor 4 (SOX4). The xenograft tumor model was used to assess the role of circ_0039411 in the tumor growth in vivo. Results Circ_0039411 was highly expressed in papillary thyroid carcinoma tissues and cell lines compared with adjacent normal tissues and NTHY-ORI3.1 cells. Circ_0039411 interference suppressed the colony formation ability, migration, invasion, and glycolysis but promoted the apoptosis of papillary thyroid carcinoma cells. MiR-423-5p was a target of circ_0039411 in papillary thyroid carcinoma cells. Circ_0039411 knockdown-mediated effects in papillary thyroid carcinoma cells were largely overturned by the silence of miR-423-5p. MiR-423-5p bound to the 3′ untranslated region (3′UTR) of SOX4. SOX4 overexpression largely reversed circ_0039411 silencing-mediated effects in papillary thyroid carcinoma cells. Circ_0039411 positively regulated SOX4 expression by sponging miR-423-5p in papillary thyroid carcinoma cells. Circ_0039411 silencing notably suppressed the growth of xenograft tumors in vivo. Conclusion Circ_0039411 promoted the malignant behaviors of papillary thyroid carcinoma cells partly depending on the regulation of the miR-423-5p/SOX4 axis.

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Hsa_circ_0000839 Inhibits Papillary Thyroid Carcinoma Proliferation by Targeting CDC27

10.21203/rs.3.rs-638595/v1 ◽

2021 ◽

Author(s):

Jiahui Guo ◽

Tingting Liu ◽

Zhongyan Shan ◽

Weiping Teng

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Molecular Mechanisms ◽

Circular Rna ◽

Luciferase Reporter ◽

Papillary Thyroid ◽

Potential Biomarker

Abstract Background: Circular RNA (circRNA) has been reported to play multiple roles in a variety of cancers. However, the role of circRNA in papillary thyroid carcinoma (PTC) remains mostly unknown. Methods: The expression, function and potential molecular mechanisms of hsa_circ_0000839 in PTC in vitro were evaluated by quantitative RT-PCR, western blot, flow cytometry, CCK8, Edu, RNA-sequencing, luciferase reporter, and RNA immunoprecipitation assay. The function of hsa_circ_0000839 in PTC in vivo was evaluated by xenograft tumors assay.Results: Hsa_circ_0000839 was significantly downregulated in PTC tissues and plasma from patients with PTC, and its downregulation was correlated with larger tumor size in patients with PTC. The role of hsa_circ_0000839 in the proliferation of PTC cell lines was evaluated in both vitro and in vivo. Mechanistically, hsa_circ_0000839 regulated the level of CDC27 via sponging miR-149-5p in PTC. Conclusions: Hsa_circ_0000839 might act as a tumor suppressor of PTC through the hsa_circ_0000839/miR-149-5p/CDC27 axis. Hsa_circ_0000839 could serve as a potential biomarker and therapeutic target for patients with PTC.

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PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma

BioMed Research International ◽

10.1155/2020/8954513 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Qin Chen ◽

Wen-Ying Yu ◽

Huan-Huan Zhang ◽

Song-Zhao Zhang ◽

Jie Fang ◽

...

Keyword(s):

Cell Proliferation ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Tumor Growth ◽

Papillary Thyroid ◽

Normal Tissues ◽

Cycle Arrest ◽

B Cell Leukemia

PBX3 (Pre-B-cell leukemia homeobox 3) had been considered to be a multifunctional oncogene which involved in tumor growth, invasion, and metastasis in leukemia and some solid tumors. However, the contribution of PBX3 to papillary thyroid carcinoma (PTC) remains unclear. In this study, we found that PBX3 expression was significantly upregulated in PTC tissues compared to adjacent normal tissues, and high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis of PTC patients. Overexpression of PBX3 in PTC cell lines promoted cell proliferation. Consistently, knockdown of PBX3 by shRNA induced cell cycle arrest at G0/G1 phase, and inhibited angiogenesis and tumor growth in vitro and in vivo. Furthermore, PBX3 promoted PTC cell proliferation and angiogenesis through activation of AT1R/VEGFR2 pathway while overexpression of AT1R and treatment with VEGFA reversed PBX3-shRNA-induced decreased phosphorylation of VEGFR2 and its downstream (ERK1/2, AKT and Src). It demonstrated that PBX3 could be used as a potential prognostic biomarker and therapeutic target for PTC.

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