circ_0005273 promotes thyroid carcinoma progression by SOX2 expression

2020 ◽  
Vol 27 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Wei Zhang ◽  
Hang Zhang ◽  
Xudong Zhao

Papillary thyroid carcinoma (PTC) is one of the most prevalent tumors in endocrine system. CircRNAs (circular RNAs) are widely known as critical regulators in tumorigenesis of papillary thyroid carcinoma (PTC). The present study focused on the functional investigation and potential molecular mechanism toward circ_0005273 in PTC progression. Gene Expression Omnibus datasets (GSE93522) and qRT-PCR (quantitative real-time PCR) analyses showed that circ_0005273 were upregulated in PTC tissues and cell lines. Moreover, circ_0005273 was located in the cytoplasm of PTC cells and suggested poor prognosis in PTC patients. In vivo and in vitro functional assays indicated that knockdown of circ_0005273 inhibited PTC tumor growth and progression, respectively. Mechanistically, miR-1183 was identified as functional target of circ_0005273, and circ_0005273 could directly bind to miR-1138 and relieve inhibition of SRY (sex-determining region Y)-box 2 (SOX2). Data from Cell Counting Kit-8, colony formation assays and transwell assays revealed that the oncogenic role of circ_0005273 on PTC progression dependent on miR-1183-mediated SOX2 expression. In conclusion, circ_0005273 functioned as a tumor promoter of PTC via circ_0005273/miR-1183/SOX2 axis, suggesting a novel biomarker and therapeutic target for PTC.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yuan-ming Jiang ◽  
Wei Liu ◽  
Ling Jiang ◽  
Hongbin Chang

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.


2017 ◽  
Vol 58 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Chen-Tian Shen ◽  
Wei-Jun Wei ◽  
Zhong-Ling Qiu ◽  
Hong-Jun Song ◽  
Xin-Yun Zhang ◽  
...  

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.


2010 ◽  
Vol 9 (7) ◽  
pp. 1968-1976 ◽  
Author(s):  
Ying C. Henderson ◽  
Yunyun Chen ◽  
Mitchell J. Frederick ◽  
Stephen Y. Lai ◽  
Gary L. Clayman

2020 ◽  
Author(s):  
Xiaolong Gui ◽  
Yan Li ◽  
Xiaobin Zhang ◽  
Ka Su ◽  
Wenlong Cao

Abstract Background: Emerging studies have demonstrated that circular RNAs (circRNAs) are key regulators for tumorigenesis in cancers, including papillary thyroid carcinoma (PTC). In this study, we aimed to explore the effects of circ_LDLR on PTC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the levels of circ_LDLR, miR-195-5p and lipase H (LIPH). RNase R digestion assay and Actinomycin D assay were utilized to analyze the characteristics of circ_LDLR. Colony formation assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay were conducted to evaluate cell proliferation. Western blot assay was used for the determination of protein levels. Flow cytometry analysis was applied to determine cell apoptosis. Transwell assay was performed to determine cell migration and invasion. Dual-luciferase reporter assay was used to verify the associations among circ_LDLR, miR-195-5p and LIPH. The murine xenograft model was constructed to explore the roles of circ_LDLR in vivo. Results: Compared to normal tissues and cells, circ_LDLR was upregulated in PTC tissues and cells. Silencing of circ_LDLR suppressed PTC cell colony formation, proliferation, migration and invasion and promoted apoptosis in vitro and hampered tumor growth in vivo. For mechanism investigation, circ_LDLR could regulate LIPH expression via sponging miR-195-5p. Moreover, miR-195-5p inhibition restored the effects of circ_LDLR knockdown on the malignant behaviors of PTC cells. MiR-195-5p overexpression inhibited PTC cell colony formation, proliferation, migration and invasion and facilitated apoptosis by targeting LIPH. Conclusion: Circ_LDLR knockdown decelerated PTC progression by regulating miR-195-5p/LIPH axis, which might provide a novel therapeutic target for PTC.


2019 ◽  
Vol 39 (1) ◽  
Author(s):  
NingHeng Chen ◽  
DeTao Yin ◽  
Bing Lun ◽  
XueLi Guo

AbstractThe aim of the present study was to investigate the potential role of GAS8 antisense RNA 1 (GAS8-AS1) in papillary thyroid carcinoma (PTC). PcDNA3.1-GAS8-AS1 and si-GAS8-AS1, miR-135b-5p mimic and si-CCND2 were transfected into PTC cells. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8). QRT-PCR was used to determine expressions of GAS8-AS1, miR-135b-5p, and CCND2, and Western blot were detected protein level of CCND2. The miRNA target gene prediction site TargetScan was used to predict potential targets of GAS8-AS1 and miR-135b-5p. Cell cycle progression was analyzed by flow cytometry. We found that GAS8-AS1 was down-regulated in PTC cell lines and inhibited proliferation and cycle of PTC cell. GAS8-AS1 directly targets miR-135b-5p, and GAS8-AS1 could regulate a downstream target of miR-135b-5p, Cyclin G2 (CCNG2), in an miR-135b-5p-mediated manner. In addition, we also proved that overexpressed GAS8-AS1 inhibited tumor formation in vivo. GAS8-AS1 suppresses PTC cell growth through the miR-135b-5p/CCND2 axis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ye Wang ◽  
Congjun Wang ◽  
Zhao Fu ◽  
Siwen Zhang ◽  
Junqiang Chen

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.


2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jing Zeng ◽  
Xiao Ma ◽  
Jinjing Wang ◽  
Ran Liu ◽  
Yun Shao ◽  
...  

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.


2021 ◽  
Author(s):  
Jiahui Guo ◽  
Tingting Liu ◽  
Zhongyan Shan ◽  
Weiping Teng

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Qin Chen ◽  
Wen-Ying Yu ◽  
Huan-Huan Zhang ◽  
Song-Zhao Zhang ◽  
Jie Fang ◽  
...  

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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