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

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.

Download Full-text

Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

10.21203/rs.3.rs-16903/v2 ◽

2020 ◽

Author(s):

Xiaolong Gui ◽

Yan Li ◽

Xiaobin Zhang ◽

Ka Su ◽

Wenlong Cao

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Colony Formation ◽

Xenograft Model ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Papillary Thyroid ◽

Cell Colony

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.

Download Full-text

Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

10.21203/rs.3.rs-16903/v1 ◽

2020 ◽

Author(s):

Xiaolong Gui ◽

Yan Li ◽

Xiaobin Zhang ◽

Ka Su ◽

Wenlong Cao

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Colony Formation ◽

Xenograft Model ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Papillary Thyroid ◽

Cell Colony

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 attempted to explore the effects of circ_LDLR on PTC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was adopted 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 employed 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 assess 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.

Download Full-text

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

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-10-0062 ◽

2010 ◽

Vol 9 (7) ◽

pp. 1968-1976 ◽

Cited By ~ 44

Author(s):

Ying C. Henderson ◽

Yunyun Chen ◽

Mitchell J. Frederick ◽

Stephen Y. Lai ◽

Gary L. Clayman

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Mek Inhibitor ◽

Carcinoma Cells ◽

Papillary Thyroid

Download Full-text

Overexpression of PAX8-AS1 Inhibits Malignant Phenotypes of Papillary Thyroid Carcinoma Cells via miR-96-5p/PKN2 Axis

International Journal of Endocrinology ◽

10.1155/2021/5499963 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Ping Zhou ◽

Tongdao Xu ◽

Hao Hu ◽

Fei Hua

Keyword(s):

Cell Proliferation ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Luciferase Reporter ◽

Human Thyroid ◽

Thyroid Cell ◽

Papillary Thyroid ◽

Western Blot Assay ◽

Proliferation And Apoptosis ◽

Relationship Of

Background. Thyroid carcinoma (THCA) is the most frequent endocrine malignancy. Papillary thyroid carcinoma (PTC) is the major subtype of THCA, accounting for over 80% of all THCA cases. LncRNA PAX8-AS1, a tumor suppressor associated with various human cancers, has been reported to be relevant to the regulation of all sorts of cellular processes. The purpose of this study was to verify the role of PAX8-AS1 in PTC. Methods. Three human PTC cell lines (K1, TPC-1, and IHH4) and one normal human thyroid cell line, Nthy-ori3-1, were used in our study. The expression of genes was detected by qRT-PCR. The bioinformatic analysis and luciferase reporter assay were used to confirm the binding relationship of PAX8-AS1 to miR-96-5p, and the targeting relationship of miR-96-5p to PKN2 was also predicted. Cell proliferation and apoptosis capacities were assessed by MTT and flow cytometry, respectively. EdU assay was used to detect cell proliferation. Western blot assay was employed to examine protein expression. Results. The expression of PAX8-AS1 was decreased in PTC tissues and cells. PAX8-AS1 overexpression inhibited the proliferation of PTC cells and promoted cell apoptosis. In addition, PAX8-AS1 bonds with miR-96-5p, whose downregulation elevated the expression of PKN2 in PTC cells. Importantly, according to the rescue experiments, PKN2 silencing partially reversed the inhibitory effects of PAX8-AS1 expression on PTC cell proliferation and apoptosis. Conclusions. We found that the PAX8-AS1/miR-96-5p/PKN2 axis was closely related to the progression of PTC, which could be a potential target for treating PTC patients.

Download Full-text

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.

Download Full-text