Papillary Thyroid Carcinoma Cell Proliferation Research Articles

NOD1 activation promotes cell apoptosis in papillary thyroid cancer

BackgroundNOD1 can promote or inhibit different types of cancers, suggesting that NOD1 functions in the progression of cancers dependent on the tumour environment. However, the expression and mechanisms of NOD1 during papillary thyroid carcinoma (PTC) progression remain unclear. MethodsTo investigate the role of NOD1 in PTC development and apoptosis, we detected NOD1 expression in three cell lines and surgical specimens from patients with PTC using immunohistochemistry, quantitative real-time PCR (Q-PCR) and Western blotting; we studied the biological functions of NOD1 by loss-of-function analysis of TPC-1 and BCPAP cells and the effect of NOD1 on the progression of PTC in terms of cell proliferation and apoptosis induced by tumour necrosis factor alpha (TNF-α), Fas ligand (Fas L), tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) or Ala-γGlu-diaminopimelic acid (TriDAP) in the presence of cycloheximide (CHX) and determined its underlying molecular mechanism using PTC cell lines in vitro and mouse xenograft models in vivo. ResultsIncreased expression of NOD1 is correlated with an improved prognosis in thyroid cancer patients. We also found that NOD1 expression was markedly upregulated in PTC cells compared to normal epithelial cells. NOD1 knockdown significantly promoted the proliferation of PTC cells in vitro, while activation of NOD1 signalling promoted PTC cell apoptosis; NOD1-induced apoptosis depends on the activation of caspase-3 and caspase-9 although the RIP2/TAK1 and MAPK pathways in PTC cells. ConclusionsThis study demonstrates that NOD1 is a predictive biomarker for PTC and that PTC cell apoptosis is induced by activation of NOD1 via the RIP2/TAK1 and MAPK pathways. The above results may provide a new perspective on targeting NOD1 signalling for the treatment of PTC, which deserves further investigation.

CircSSU72 Promotes Cell Proliferation, Migration and Invasion of Papillary Thyroid Carcinoma Cells by Targeting miR-451a/S1PR2 Axis.

Introduction: Thyroid cancer is the most common endocrine malignancy with Papillary Thyroid Carcinoma (PTC) as the most common pathological type. Due to low mortality but a high incidence, PTC still causes a relatively heavy burden on financial costs, human health, and quality of life. Emerging researches have indicated that circular RNAs (circRNAs) play a significant regulatory role in various cancers, including PTC. However, the functions and mechanisms of circRNAs derived from SSU72 remain unknown. Method: The expression level of circRNAs derived from the exons of SSU72, miR-361–3p, miR-451a, and S1PR2 was evaluated by qRT-PCR assay or western blot assay. The interactions between circSSU72 (hsa_circ_0009294), miR-451a, and S1PR2 were verified by dual-luciferase reporter assay. Effects of circSSU72, miR-451a, and S1PR2 on cell proliferation, migration, and invasion were confirmed by colony formation assay, cell counting kit-8 (CCK-8), wound healing assay, and Transwell assays in vitro. Results: circSSU72 was upregulated in PTC; circSSU72 knockdown inhibited PTC cell proliferation, migration, and invasion. In addition, circSSU72 could negatively regulate miR-451a by functioning as a sponge. circSSU72 promoted PTC cell proliferation, migration, and invasion by targeting miR-451a in vitro. We further found that miR-451a inhibited PTC cell proliferation, migration, and invasion by regulating S1PR2. Overall, the circSSU72/miR-451a/S1PR2 axis might influence PTC cell proliferation, migration, and invasion. Conclusions: Overall, circSSU72 (hsa_circ_0009294)/miR-451a/S1PR2 axis may promote cell proliferation, migration, and invasion in PTC. Thus, circSSU72 may serve as a potential biomarker and therapeutic target for PTC.

LMO3 promotes proliferation and metastasis of papillary thyroid carcinoma cells by regulating LIMK1-mediated cofilin and the β-catenin pathway.

LIM domain only 3 (LMO3) interacts with transcription factors to regulate target genes involved in embryonic development. The oncogenic role of LMO3 in hepatocellular carcinoma, gastric cancer, and neuroblastoma has been reported recently. However, little is known about the biological function of LMO3 in papillary thyroid carcinoma (PTC). First, expression of LMO3 was dramatically enhanced in the PTC tissues and cell lines. Second, knockdown of LMO3 in PTC cells repressed cell proliferation and promoted cell apoptosis with downregulated Bcl-2 and upregulated cleaved caspase-3/PARP. In vitro cell migration and invasion of PTC were also retarded by siRNA-mediated silence of LMO3. Third, protein expression of LIM kinase (LIMK) 1-mediated phosphorylation of cofilin and nuclear translocation of β-catenin were reduced by the knockdown of LMO3. pcDNA-mediated overexpression of LIMK1 promoted cofilin phosphorylation and attenuated LMO3 silence-induced decrease of cofilin phosphorylation. Last, enhanced LIMK1 expression promoted PTC cell proliferation and metastasis and counteracted the suppressive effects of LMO3 silence on PTC cell proliferation and metastasis. In conclusion, LMO3 promoted PTC cell proliferation and metastasis by regulating LIMK1-mediated cofilin and the β-catenin pathway.

RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the main type of thyroid carcinoma. Despite the good prognosis, some PTC patients may deteriorate into more aggressive diseases, leading to poor survival. Molecular technology has been increasingly used in the diagnosis and treatment of thyroid carcinoma. In this study, we identified that RNA Binding Motif Protein 47 (RBM47) was downregulated in PTC tissues and cells, and overexpression of RBM47 could activate autophagy and inhibit proliferation in PTC cells. RBM47 promotes but can not bind directly to Forkhead Box O3 (FOXO3). FOXO3 activates Autophagy Related Gene 3 (ATG3), ATG5, and RBM47 to form a loop and promote autophagy. RBM47 can bind directly to and stabilized lncRNA Small Nucleolar RNA Host Gene 5 (SNHG5) to inhibit PTC cells proliferation and activate autophagy in vitro and in vivo. SNHG5 inhibits ubiquitination and degradation of FOXO3 by recruiting Ubiquitin Specific Peptidase 21 (USP21), then promotes the translocation of FOXO3 from cytoplasm to nucleus. Our study revealed the regulatory mechanism of RBM47/SNHG5/FOXO3 axis on cell proliferation and autophagy in PTC, which may provide valuable insight for the treatment of PTC.

Semaphorin 3D inhibits proliferation and migration of papillary thyroid carcinoma by regulating MAPK/ERK signaling pathway.

Semaphorin 3D (SEMA3D) plays an important role in the occurrence and development of multifarious cancers. However, the relationship between SEMA3D and papillary thyroid carcinoma (PTC) remains unclear. This study aimed to investigate the functions and mechanism of SEMA3D in papillary thyroid carcinoma (PTC). The expression of SEMA3D in PTC tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blotting and immunohistochemistry (IHC) were used to detect the expression of the related proteins. CCK-8 and colony formation assays and Transwell assays were used to evaluate cell proliferation and migration, respectively. A xenograft model was induced to further verify the effect of SEMA3D in vivo. In this study, we found that SEMA3D was downregulated in PTC tissues and PTC cell lines (TPC-1 and BCPAP). The expression level of SEMA3D was significantly related to age (P < 0.01), extrathyroidal extension (P < 0.01), TNM stage (P < 0.01) and lymph node metastasis (P < 0.01). In vitro experiments showed that overexpression of SEMA3D inhibited the proliferation and migration of TPC-1 and BCPAP cells and that upregulated SEMA3D inhibited the phosphorylation of ERK and the expression of the phenotype-related proteins PCNA and MMP2. In addition, SEMA3D overexpression inhibited tumour growth in vivo. In this study, we found that SEMA3D is significantly downregulated in PTC tissues. SEMA3D inhibits the proliferation and migration of PTC cells and suppresses tumour growth in vivo, possibly partially through the MAPK/ERK signalling pathway, suggesting that SEMA3D may be a reliable molecular marker for the diagnosis and treatment of PTC.

TRNA-Derived Fragment tRF-18 Facilitates Cell Proliferation and Inhibits Cell Apoptosis via Modulating KIF1B in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC), a common malignancy, poses a threat to human health. It has been identified that tRNA-derived fragments (tRFs) can be new putative biomarkers and targets for cancer treatment. The object of this research was to investigate the biological role and mechanism of main tRF-18-H7PU4HD2 (tRF-18) in PTC. The biological effects of tRF-18 on PTC cell proliferation and apoptosis were explored by Cell Counting Kit-8 assays, colony formation assays, and flow cytometry analysis. Additionally, Western blot analysis was performed to quantify protein levels of apoptotic markers in PTC cells. Moreover, xenograft model in nude mice was established to investigate the impact of tRF-18 on tumor growth in vivo. The interaction between tRF-18 and messenger RNA kinesin family member 1B (KIF1B) was validated via RNA immunoprecipitation assays and luciferase reporter assays. tRF-18 exhibited high expression in PTC tissues. Further, the upregulation of tRF-18 was also detected in TPC-1 and IHH4 cell lines. Importantly, tRF-18 inhibition restrained PTC cell proliferation and promoted cell apoptosis. In addition, tRF-18 inhibition suppressed xenograft tumor growth. Mechanistically, tRF-18 was confirmed to target KIF1B and negatively regulate KIF1B expression in PTC cells. tRF-18 facilitates PTC cell proliferation and inhibits cell apoptosis by targeting KIF1B.

CircLDLR Promotes Papillary Thyroid Carcinoma Tumorigenicity by Regulating miR-637/LMO4 Axis

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.

Tripartite Motif Containing 3 inhibits the aggressive behaviors of papillary thyroid carcinoma and indicates lower recurrence risk.

Tripartite Motif Containing 3 (TRIM3) has been reported to be downregulated in several malignancies. However, its prognostic significance in thyroid cancer remains unknown. Here we aimed to investigate TRIM3's expression and its involvement in papillary thyroid carcinoma (PTC). Clinicopathological analyses were performed in patients with PTC. Expression of TRIM3 protein was evaluated by IHC. The prognostic role of TRIM3 in PTC patients was assessed by univariate and multivariate analyses. Cell proliferation and invasion were tested in two PTC cell lines following overexpression or knockdown. TRIM3 was decreased in PTC tissues compared to adjacent thyroid tissues on both mRNA and protein levels. Additionally, low expression of TRIM3 was significantly related to tumor size, lymph node metastasis and TNM stage. Moreover, TRIM3 was identified as an independent prognosis factor by multivariate analysis. Cellular data revealed that TRIM3 can inhibit the proliferation and invasion of PTC cells. Consistently, TRIM3 can upregulate the expression level of E-cadherin, while downregulate N-cadherin, Vimentin, and cyclin D1 expression. TRIM3 expression was downregulated in PTC tissues comparing with that in adjacent nontumorous thyroid tissues. Lower TRIM3 expression in PTC can contribute independently to a poorer prognosis by enhancing PTC proliferation and invasion, highlighting its potential as a novel therapeutic target and prognostic biomarker.

MiR-222-3p promotes the proliferation, migration and invasion of papillary thyroid carcinoma cells through targeting SLC4A4.

An increasing number of studies indicate that miR-222-3p is upregulated in various cancers and can regulate tumor progression. This study aimed to explore the regulatory mechanism of miR-222-3p in papillary thyroid carcinoma (PTC). TCGA database was used to dig differentially expressed miRNAs and mRNAs in PTC tissue. Relevant references were searched to determine target miRNA. StarBase, TargetScan and miRDB were applied to predict mRNAs that had binding sites with the target miRNA. Then, the mRNAs were intersected with differentially downregulated mRNAs in TCGA to determine the target mRNA. qRT-PCR was exerted to evaluate gene expression of miR-222-3p and SLC4A4 in PTC. Western blot was performed out to evaluate the protein expression of SLC4A4 in PTC cells. CCK-8, wound healing assay and cell invasion assay were undertaken to observe the proliferative, migratory, and invasive abilities of PTC cells. Dual-luciferase assay was employed to test the binding relationship between miR-222-3p and SLC4A4. MiR-222-3p was highly expressed in PTC while SLC4A4 was lowly expressed. Moreover, miR-222-3p was able to promote the proliferation, invasion, and migration of PTC cells. SLC4A4 was able to reverse these promotive effects of miR-222-3p. MiR-222-3p can promote the proliferation, migration and invasion of PTC cells through targeting SLC4A4. MiR-222-3p is expected to be a molecular therapeutic target for PTC patients.

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

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.

CircRNA NRIP1 promotes papillary thyroid carcinoma progression by sponging mir-195-5p and modulating the P38 MAPK and JAK/STAT pathways

BackgroundCircular RNAs (circRNAs) have become a hot topic in the area of tumor biology due to its closed structure and the post-transcriptional regulatory effect. This study aims to clarify the roles of circRNA nuclear receptor-interacting protein 1 (NRIP1; circNRIP1) and the possible mechanisms in papillary thyroid carcinoma (PTC).MethodsThe real-time PCR was used to detect the expression level of CircRNA NRIP1 in PTC specimens and cell lines. The effects of CircRNA NRIP1 and miR-195-5p on the PTC cell functions were detected by MTT, transwell, and flow cytometry assays. Dual-luciferase reporter assays and pull down assays were used to verify the association between circRNA NRIP1 and miR-195-5p. The murine xenograft models were constructed to detect the roles of CircRNA NRIP1 and miR-195-5p. Western blot was applied to detect the effects of CircRNA NRIP1 and miR-195-5p on the P38 MAPK and JAK/STAT singling pathways.ResultsCircRNA NRIP1 was over-expressed in PTC tissues and cells and the high levels of CircRNA NRIP1 were correlated with advanced PTC stage. Depletion of CircRNA NRIP1 inhibited PTC cell proliferation, invasion, while accelerated apoptosis. miR-195-5p upregulation repressed proliferation and invasion capabilities, and accelerated apoptosis of PTC cell lines and restraining the growth of tumor xenografts, while the functions were reversed following CircRNA NRIP1 overexpression in PTC cells and tumor xenografts. Besides, the protein levels of p-p38, p-JAK2 and p-STAT1 were remarkably down-regulated in miR-195-5p overexpressed PTC cells and tumor xenografts, whereas CircRNA NRIP1 up-regulation overturned the impacts.ConclusionsIn conclusion, CircRNA NRIP1 promoted PTC progression by accelerating PTC cells proliferation, invasion and tumor growth, while impeding apoptosis by way of sponging miR-195-5p and regulating the P38 MAPK and JAK/STAT pathways.

LncRNA NORAD promotes thyroid carcinoma progression by targeting miR-451.

Long non-coding RNA (lncRNA) NORAD plays an essential role in the development and progress of papillary thyroid carcinoma (PTC). MicroRNA-451 (MiR-451) has been identified as playing an inhibitory role in some types of cancer. However, the molecular mechanism of lncRNA NORAD regulating metastasis of PTC cells by miR-451 has not been fully elucidated. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) or Western blot analysis of the expression of NORAD, miR-451, and interleukin-6 receptor (IL-6R) in PTC cell lines were carried out. The detection of Luciferase reporter gene showed the relationship between lncRNA NORAD, miR-451 and IL-6R. Cell Counting Kit-8 (CCK-8) assay and transwell assay were performed to detect the influence of lncRNA NORAD, miR-451 on the proliferation, migration, and invasion of PTC cells. The results of RT-qPCR and Western blotting suggested that the expression of lncRNA NORAD and IL-6R were higher than that of the control group, while the expression of miR-451 was lower. Transwell assay indicated that the knockdown of lncRNA NORAD or overexpression of miR-451 significantly inhibited cell proliferation, migration and invasion in PTC cell lines. In addition, lncRNA NORAD negatively controls the expression of miR-451, resulting in the upregulation of IL-6R. IL-6R overexpression can reverse the inhibitory effect of lncRNA NORAD knockdown or miR-451 on PTC cell proliferation and metastasis. Our results indicated that the cell migration and invasion were inhibited by knockdown of lncRNA NORAD or overexpression of miR-451, suggesting that the axis of lncRNA NORAD -miR-451- IL-6R was involved in the development of PTC.

Cervical carcinoma high-expressed long non-coding RNA 1 promotes papillary thyroid carcinoma cell proliferation and invasion.

BackgroundStudies have shown that cervical carcinoma high-expressed long non-coding RNA 1 (lncRNA-CCHE1) may promote tumor development by regulating tumor migration and invasion in a variety of cancers; yet, the role of lncRNA-CCHE1 in papillary thyroid carcinoma (PTC) remains unclear. The purpose of this study was to explore the mechanism of lncRNA-CCHE1 in PTC.MethodsThe expression of lncRNA-CCHE1 in 51 PTC carcinoma tissues and normal adjacent tissues was measured using real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK8), plate cloning assay, transwell assay, and flow cytometry were used to analyze the effect of lncRNA-CCHE1 on PTC cell proliferation, invasion, and apoptosis in vitro.ResultsA higher expression of lncRNA-CCHE1 was found in PTC tissues than in adjacent tissues. High expression of lncRNA-CCHE1 was positively correlated with the number of tumors, extra-glandular invasion, and tumor stage. In addition, the down-regulation of lncRNA-CCHE1 reduced the proliferation and invasion of PTC cell lines and promoted cell apoptosis, while its up-regulation caused the opposite effect. These effects were regulated via the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway.ConclusionsThe lncRNA-CCHE1 is closely related to PTC progression and may be used as a potential biomarker for early diagnosis and treatment of PTC.

LncRNA CASC15 promotes the proliferation of papillary thyroid carcinoma cells by regulating the miR-7151–5p/WNT7A axis

Long noncoding RNAs (lncRNAs) play crucial roles in the regulation of human thyroid cancer (TC), including papillary thyroid carcinoma (PTC); PTC is the most common pathological subtype of TC. To date, the expression, function, and mechanism of the lncRNA CASC15 in PTC remain unclear. The present study results showed that CASC15 was overexpressed in PTC tissues compared with normal tissues and acted as a potent oncogene to promote the proliferation and tumorigenesis of PTC cells both in vitro and in vivo. Mechanistic studies demonstrated that CASC15 could serve as an endogenous miRNA sponge to absorb and downregulate miR-7151–5p, thereby preventing the inhibition of WNT7A during PTC progression. Furthermore, the study demonstrated that CASC15 activated the WNT/β‑catenin signaling pathway by upregulating WNT7A in PTC. Taken together, our findings identified CASC15 as a potential diagnostic marker or therapeutic target for PTC progression. Data AvailabilityPlease contact the corresponding author for a data request.

Long noncoding RNA ILF3-AS1 aggravates papillary thyroid carcinoma progression via regulating the miR-4306/PLAGL2 axis

BackgroundIt have been proven that long non-coding RNAs (lncRNAs) serve as regulators in carcinogenesis. Interleukin enhancer binding factor 3 antisense RNA 1 (ILF3-AS1) has been illuminated as a prognostic factor in some cancers. Nevertheless, its expression pattern and possible functions in papillary thyroid carcinoma (PTC) have not been studied.MethodsThe expression of ILF3-AS1 was measured by RT-qPCR and ISH. Colony formation assay and EdU assay were used to probe cell proliferation. TUNEL assay was used for analysis of cell apoptosis. Immunofluorescence and western blot were conducted to evaluate the expression change of E-cadherin and N-cadherin. The RNA interaction was demonstrated by mechanism experiments, including pull down assay and dual luciferase reporter assay.ResultsILF3-AS1 expression was evidently upregulated in PTC cell lines. ILF3-AS1 knockdown restrained the proliferation, migration and invasion of PTC cells. Mechanical investigation revealed that miR-4306 could interact with ILF3-AS1. PLAGL2 was a downstream target of miR-4306. The effects of ILF3-AS1 knockdown on the cellular processes were abrogated by miR-4306 downregulation or pleiomorphic adenoma gene-like 2 (PLAGL2) overexpression.ConclusionILF3-AS1 plays tumor-promoting role in PTC via targeting miR-4306/PLAGL2 axis.

MicroRNA-181a promotes the oncogene S100A2 and enhances papillary thyroid carcinoma growth by mediating the expression of histone demethylase KDM5C.

Papillary thyroid carcinoma (PTC) is an endocrine malignancy. Increasing evidence highlights microRNAs (miRNAs) as important participants in PTC. Here, we investigated the role of miR-181a in PTC. A microarray-based analysis was performed to identify the differential expression of miR-181a in PTC, which was validated with RT-qPCR. Protein expression of the proliferation-related factor Ki-67 and apoptosis- and migration-related factors in PTC was assessed with immunoblot analysis. A dual-luciferase reporter gene assay was adopted to verify the relationship between miR-181a and lysine demethylase 5C (KDM5C). Chromatin immunoprecipitation (ChIP) was used to detect the level of the H3K4me3 modification on S100 calcium-binding protein A2 (S100A2). Cell viability, apoptosis, and invasion and migration abilities were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays, respectively. The in vitro results were verified in in vivo nude mouse models. miR-181a was highly expressed in PTC tissues and cell lines. Silencing miR-181a repressed the proliferation and migration of PTC cells. KDM5C was identified as the target gene of miR-181a and represses S100A2 expression through histone demethylation to diminish the migration and proliferation of PTC cells. miR-181a depletion suppressed tumor growth. Collectively, these results suggest that highly expressed miR-181a promotes the proliferation of PTC cells by increasing the expression of the oncogene S100A2. This study contributes to the advancement of miR-181a-targeted therapeutics.

EGR1/2 Inhibits Papillary Thyroid Carcinoma Cell Growth by Suppressing the Expression of PTEN and BAX.

Early growth response (EGR) proteins have been reported to be involved in cell growth and apoptosis in a variety of cancer types and could inhibit tumor development. However, the role of EGR1/2 in papillary thyroid carcinoma (PTC) has not been elucidated. The expression pattern of EGR1/2 in adjacent tissues and cancer tissues and the clinical prognosis of EGR1/2 were analyzed by using the samples from TCGA database. The cell viability was detected by MTT assay. Luciferase reporter assay was used to demonstrate the binding of EGR1/2 to the target gene promotor region. Our results showed that EGR1/2 was significantly downregulated in tumor tissues and correlated with poor prognosis. Overexpression of EGR1/2 inhibited proliferation of IHH-4 and BCPAP cells, and knockdown of EGR1/2 showed a reverse effect. Overexpression of EGR1 or EGR2 promoted phosphatase and tension homolog (PTEN) or Bcl-2-associated X (BAX) expression, and EGR1 or EGR2 was able to directly bind to the promoter region of PTEN or BAX. In conclusion, we found that the altered expression of EGR1/2 affected the proliferation of PTC cells and regulated the expression of PTEN and BAX.

FK506-binding protein 5 promotes the progression of papillary thyroid carcinoma.

ObjectiveTo detect the expression of FK506-binding protein 5 (FKBP5) in human papillary thyroid carcinoma (PTC) tissues, and explore its possible role in the progression of PTC.MethodsFKBP5 expression levels were assessed in 115 PTC tissues and corresponding normal tissues by immunohistochemistry. We also examined the correlations between FKBP5 expression and clinicopathological factors and survival in 75 patients with PTC. The effects of FKBP5 on the proliferation and apoptosis of PTC cells were detected by colony-formation, MTT, and flow cytometry assays, respectively. We further investigated the effects of FKBP5 on tumor growth in mice.ResultsWe revealed high expression levels of FKBP5 in human PTC tissues compared with normal tissues. Furthermore, high FKBP5 expression was associated with an increased incidence of intraglandular dissemination, and lower overall and progression-free survival. FKBP5 depletion remarkably suppressed the proliferation and induced apoptosis of PTC cells in vitro. FKBP5 further contributed to the growth of PTC tumors in mice.ConclusionsThe results of this study demonstrated the potential involvement of FKBP5 in the progression of PTC, and confirmed FKBP5 as a novel therapeutic target for PTC treatment.

Anti-proliferative and apoptotic effects of hull-less pumpkin extract on human papillary thyroid carcinoma cell line.

Papillary thyroid carcinoma (PTC) is one of the most common cancers of the endocrine system. Previous studies have shown that the extract of hull-less pumpkin seed (HLPS) has a significant anti-cancer effect. The aim of this study was to evaluate the effect of this plant extract on the proliferation of PTC cells. In this study, an extract of this plant was prepared by soxhlet extraction method and analyzed by Gas Chromatography-Mass Spectrometry. The cytotoxicity of PTX and plant extract was investigated using the methylthiazol tetrazolium (MTT) method. For careful investigation of morphological alteration, we used hematoxylin and eosin and Giemsa stinging. Based on MTT assay test, the IC50 value of paclitaxel (PTX) was significantly less than the hydro-alcoholic extract of HLPS at all of the incubation time. Our results of histological staining showed that HLPS and PTX induced significant morphological alteration in the PTC cultured cell that consistent with cell death. Comparing the groups treated by PTX or HLPS with control group showed significant differences. It seems that HLPS extract has an apparent effect on treatment of PTC, at least in laboratory condition, albeit for realistic decision about the effect of HLPS on PTC, more molecular investigations are necessary.

SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with a rapidly increasing incidence globally. Bioinformatics analyses suggested that SHCBP1 (SHC SH2 Domain-Binding Protein 1) was significantly up-regulated in PTC tumor tissues, which was further confirmed by immunohistochemical staining and qPCR analyses in Xuzhou cohort. Moreover, the results indicated that the mRNA level of SHCBP1 was negatively associated with patients’ disease-free survival rate, and further analysis reveals that patients with high SHCBP1 expression tend to have more lymph node metastasis. Afterward, MTT, colony formation, cell-cycle assay, FACS apoptosis assay, invasion, migration, as well as scratch assay were performed to study the phenotypes change of PTC cells after knocking down SHCBP1. The in vivo subcutaneous tumor model was developed to study the proliferation ability of PTC cells after SHCBP1 knockdown. We show that knock down of SHCBP1 significantly inhibits PTC cell proliferation, cell cycle, invasion and migration in vivo and in vitro. Western blot and qRT-PCR showed that knockdown of SHCBP1 could significantly reduce MYC, KLF4, CD44, ITGA6, ITGB1, ITGB5, and COL4A2 expression at both RNA and protein levels, which indicated that SHCBP1 might be involved in PTC carcinogenesis and progression through targeting formation of integrin and collagen and cell stemness pathways, and can be a potential diagnosis biomarker and therapeutic target for PTC.