KiSS1 suppresses TNFα‐induced breast cancer cell invasion via an inhibition of RhoA‐Mediated NF‐κB activation

Tumor necrosis factor‐alpha (TNFα) induces cancer development and metastasis, which is prominently achieved by nuclear factor‐kappa B (NF‐κB) activation. TNFα‐induced NF‐κB activation enhances cellular mechanisms including proliferation, migration, and invasion. KiSS1, a key regulator of puberty, was initially discovered as a tumor metastasis suppressor. The expression of KiSS1 was lost or down‐regulated in different metastatic tumors. However, it is unclear whether KiSS1 regulates TNFα‐induced NF‐κB activation and further tumor cell migration. In this study, we demonstrate that KiSS1 suppresses the migration of breast cancer cells by inhibiting TNFα‐induced NF‐κB pathway and RhoA activation. Both KiSS1 overexpression and KP10 (kisspeptin‐10) stimulation inhibited TNFα‐induced NF‐κB activity, suppressed TNFα‐induced cell migration and cell attachment to fibronectin in breast cancer cells while KP10 has little effect on cancer cell proliferation. Furthermore, KP10 inhibited TNFα‐induced cell migration and RhoA GTPase activation. Therefore, our data demonstrate that KiSS1 inhibits TNFα‐induced NF‐κB activation via downregulation of RhoA activation and suppression of breast cancer cell migration and invasion. J. Cell. Biochem. 107: 1139–1149, 2009. © 2009 Wiley‐Liss, Inc.     

Arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP-9 induction

Arachidonate 5-lipoxygenase (ALOX5) expression and activity has been implicated in tumor pathogenesis, yet its role in papillary thyroid carcinoma (PTC) has not been characterized. ALOX5 protein and mRNA were upregulated in PTC compared to matched, normal thyroid tissue, and ALOX5 expression correlated with invasive tumor histopathology. Evidence suggests that PTC invasion is mediated through the induction of matrix metalloproteinases (MMPs) that can degrade and remodel the extracellular matrix (ECM). A correlation between MMP-9 and ALOX5 protein expression was established by immunohistochemical analysis of PTC and normal thyroid tissues using a tissue array. Transfection of ALOX5 into a PTC cell line (BCPAP) increased MMP-9 secretion and cell invasion across an ECM barrier. The ALOX5 product, 5(S)-hydroxyeicosatetraenoic acid also increased MMP-9 protein expression by BCPAP in a dose-dependent manner. Inhibitors of MMP-9 and ALOX5 reversed ALOX5-enhanced invasion. Here we describe a new role for ALOX5 as a mediator of invasion via MMP-9 induction; this ALOX5/MMP9 pathway represents a new avenue in the search for functional biomarkers and/or potential therapeutic targets for aggressive PTC.     

Downregulation of uPAR inhibits migration,invasion, proliferation,FAK/PI3K/Akt signaling and induces senescence in papillary thyroid carcinoma cells

Papillary thyroid carcinoma (PTC) is the most common endocrine and thyroid malignancy. The urokinase plasminogen activator receptor (uPAR) plays an important role in cancer pathogenesis, including breakdown of the extracellular matrix, invasion, and metastasis. Additionally, there is increasing evidence that uPAR also promotes tumorigenesis via the modulation of multiple signaling pathways. BRAFV600E, the most common initial genetic mutation in PTC, leads to ERK1/2 hyperphosphorylation, which has been shown in numerous cancers to induce uPAR. Treatment of the BRAFV600E-positive PTC cell line, BCPAP, with the MEK/ERK inhibitor U0126 reduced uPAR RNA levels by 90%. siRNA-mediated down-regulation of uPAR in BCPAP cells resulted in greatly decreased activity in the focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This phenomenon was concurrent with drastically reduced proliferation rates and decreased clonigenic survival, as well as demonstrated senescence-associated nuclear morphology and induction of b-galactosidase activity. uPAR-knockdown BCPAP cells also displayed greatly reduced migration and invasion rates, as well as a complete loss of the cells' ability to augment their invasiveness following plasminogen supplementation. Taken together, these data provide new evidence of a novel role for uPAR induction (as a consequence of constitutive ERK1/2 activation) as a central component in PTC pathogenesis, and highlight the potential of uPAR as a therapeutic target.     

Growth‐associated protein 43 promotes thyroid cancer cell lines progression via epithelial‐mesenchymal transition

Thyroid cancer is maintaining at a high incidence level and its carcinogenesis is mainly affected by a complex gene interaction. By analysis of the next‐generation resequencing of paired papillary thyroid cancer (PTC) and adjacent thyroid tissues, we found that Growth Associated Protein 43 (GAP43), a phosphoprotein activated by protein kinase C, might be novel markers associated with PTC. However, its function in thyroid carcinoma has been poorly understood. We discovered that GAP43 was significantly overexpressed in thyroid carcinoma and these results were consistent with that in The Cancer Genome Atlas (TCGA) cohort. In addition, some clinicopathological features of GAP43 in TCGA database showed that up‐regulated GAP43 is significantly connected to lymph node metastasis (P < 0.001) and tumour size (P = 0.038). In vitro experiments, loss of function experiments was performed to investigate GAP43 in PTC cell lines (TPC‐1 and BCPAP). The results proved that GAP43 knockdown in PTC cell significantly decreased the function of cell proliferation, colony formation, migration, and invasion and induced cell apoptosis. Furthermore, we also indicated that GAP43 could modulate the expression of epithelial‐mesenchymal transition‐related proteins, which could influence invasion and migration. Put those results together, GAP43 is a gene which was associated with PTC and might be a potential therapeutic target.     

Downregulation of uPAR inhibits migration,invasion, proliferation,FAK/PI3K/Akt signaling and induces senescence in papillary thyroid carcinoma cells

Papillary thyroid carcinoma (PTC) is the most common endocrine and thyroid malignancy. The urokinase plasminogen activator receptor (uPAR) plays an important role in cancer pathogenesis, including breakdown of the extracellular matrix, invasion and metastasis. Additionally, there is increasing evidence that uPAR also promotes tumorigenesis via the modulation of multiple signaling pathways. BRAF^V600E, the most common initial genetic mutation in PTC, leads to ERK1/2 hyperphosphorylation, which has been shown in numerous cancers to induce uPAR. Treatment of the BRAF^V600E-positive PTC cell line, BCPAP, with the MEK/ERK inhibitor U0126 reduced uPAR RNA levels by 90%. siRNA-mediated downregulation of uPAR in BCPAP cells resulted in greatly decreased activity in the focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This phenomenon was concurrent with drastically reduced proliferation rates and decreased clonigenic survival, as well as demonstrated senescence-associated nuclear morphology and induction of β-galactosidase activity. uPAR-knockdown BCPAP cells also displayed greatly reduced migration and invasion rates, as well as a complete loss of the cells'' ability to augment their invasiveness following plasminogen supplementation. Taken together, these data provide new evidence of a novel role for uPAR induction (as a consequence of constitutive ERK1/2 activation) as a central component in PTC pathogenesis, and highlight the potential of uPAR as a therapeutic target.Key words: urokinase plasminogen activator receptor (uPAR), papillary thyroid carcinoma, invasion, migration, proliferation, senescence, FAK, PI3K, Akt     

Dauricine induces apoptosis,inhibits proliferation and invasion through inhibiting NF‐κB signaling pathway in colon cancer cells

Dauricine, a bioactive component of Asiatic Moonseed Rhizome, has been widely used to treat a large number of inflammatory diseases in traditional Chinese medicine. In our study, we demonstrated that dauricine inhibited colon cancer cell proliferation and invasion, and induced apoptosis by suppressing nuclear factor‐kappaB (NF‐κB) activation in a dose‐ and time‐dependent manner. Addition of dauricine inhibited the phosphorylation and degradation of IκBα, and the phosphorylation and translocation of p65. Moreover, dauricine down‐regulated the expression of various NF‐κB‐regulated genes, including genes involved cell proliferation (cyclinD1, COX2, and c‐Myc), anti‐apoptosis (survivin, Bcl‐2, XIAP, and IAP1), invasion (MMP‐9 and ICAM‐1), and angiogenesis (VEGF). In athymic nu/nu mouse model, we further demonstrated that dauricine significantly suppressed colonic tumor growth. Taken together, our results demonstrated that dauricine inhibited colon cancer cell proliferation, invasion, and induced cell apoptosis by suppressing NF‐κB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of dauricine in preventing or treating colon cancer through modulation of NF‐κB singling pathway. J. Cell. Physiol. 225: 266–275, 2010. © 2010 Wiley‐Liss, Inc.     

Platycodin D,a triterpenoid saponin from Platycodon grandiflorum,suppresses the growth and invasion of human oral squamous cell carcinoma cells via the NF‐κB pathway

This work was undertaken to explore the effects of platycodin D, a triterpenoid saponin from Platycodon grandiflorum, on the growth and invasiveness of human oral squamous cell carcinoma (OSCC). Platycodin D caused a significant, concentration‐dependent inhibition of cell viability and induced significant apoptosis in OSCC cells. Moreover, platycodin D significantly inhibited OSCC cell invasion. At the molecular level, platycodin D increased the amounts of IκBα protein and reduced the expression of phosphorylated NF‐κB p65, MMP‐2, and MMP‐9. Ectopic expression of constitutively active NF‐κB p65 prevented platycodin D‐mediated induction of apoptosis and suppression of invasion in OSCC cells. In vivo studies confirmed that platycodin D retarded the growth of subcutaneous SCC‐4 xenograft tumors and reduced phosphorylation of NF‐κB p65. Altogether, platycodin D shows inhibitory activity on OSCC growth and invasion through inactivation of the NF‐κB pathway and might provide therapeutic benefits in the treatment of OSCC.     

Geraniin suppresses ovarian cancer growth through inhibition of NF‐κB activation and downregulation of Mcl‐1 expression

This study investigated the anticancer effects of geraniin on ovarian cancer cells and the signaling pathways involved. Ovarian cancer cells were treated with different concentrations of geraniin for 48 h and examined for viability, apoptosis, mitochondrial membrane depolarization, and gene expression. Xenograft tumor studies were performed to determine the anticancer activity of geraniin in vivo. Geraniin significantly decreased cancer cell viability in a concentration‐dependent fashion. Geraniin significantly triggered apoptosis, which was accompanied by loss of mitochondrial membrane potential and increased cytochrome c release and caspsase‐3 activity. Mechanistically, geraniin significantly downregulated Mcl‐1 and impaired NF‐κB p65 binding to the mcl‐1 promoter. Overexpression of Mcl‐1 significantly reversed geraniin‐induced apoptosis in OVCAR3 cells. In addition, geraniin retarded ovarian cancer growth and reduced expression of phospho‐p65 and Mcl‐1. Collectively, geraniin elicits growth suppression in ovarian cancer through inhibition of NF‐κB and Mcl‐1 and may provide therapeutic benefits for this malignancy.     

LINC00667 promotes Wilms’ tumor metastasis and stemness by sponging miR‐200b/c/429 family to regulate IKK‐β

Wilms' tumor, also known as nephroblastoma, is a kind of pediatric renal cancer. Previous studies have indicated that microRNAs (miRNAs) regulate various cancers progression. However, whether miR‐200 family regulated Wilms' tumor progression remains to be elucidated. In our study, miR‐200b/c/429 expression was downregulated in Wilms' tumor tissue samples from 25 patients. And data from three independent analyses of quantitative real‐time polymerase chain reaction revealed that the expression of miR‐200b/c/429 was downregulated in Wilms' tumor cell lines. Functionally, Cell counting kit‐8 assay revealed that cell viability was reduced by overexpressing miR‐200b/c/429. Transwell assay manifested that cell migration and invasion was hindered by miR‐200b/c/429 overexpression. Sphere‐forming and western blot assays demonstrated that miR‐200b/c/429 overexpression suppressed the sphere formation ability. Mechanically, nuclear factor‐κB (NF‐κB) pathway was confirmed to be associated with Wilms' tumor progression; miR‐200b/c/429 overexpression inactivated NF‐κB pathway as miR‐200b/c/429 was identified to target IκB kinase β (IKK‐β), an NF‐κB pathway‐related gene. Moreover, miR‐200b/c/429 was sponged by LINC00667 in Wilms' tumor cells. LINC00667 competitively bound with miR‐200b/c/429 to regulate IKK‐β expression and then activated NF‐κB pathway in Wilms' tumor. Subsequently, rescue assays illustrated that silencing of IKK‐β could reverse the effect of miR‐200b/c/429 inhibition on the progression of sh‐LINC00667‐transfected Wilms' tumor cells. In summary, LINC00667 promoted Wilms' tumor progression by sponging miR‐200b/c/429 family to regulate IKK‐β.     

Modulation of Activation-Induced Cytidine Deaminase by Curcumin in Helicobacter pylori-Infected Gastric Epithelial Cells

Background: Anomalous expression of activation‐induced cytidine deaminase (AID) in Helicobacter pylori‐infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)‐κB activation by H. pylori and hence, inhibition of NF‐κB pathway can downregulate the expression of AID. Curcumin, a spice‐derived polyphenol, is known for its anti‐inflammatory activity via NF‐κB inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF‐κB inhibitory activity in H. pylori‐infected gastric epithelial cells. Materials and Methods: MKN‐28 or MKN‐45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co‐culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme‐linked immunosorbent assay was performed to evaluate the anti‐adhesion activity of curcumin. Real‐time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF‐κB, inhibitors of NF‐κB (IκB), and IκB kinase (IKK) complex regulation with or without curcumin. Results: The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (≤10 μmol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF‐κB activation inhibitor (SN‐50) and proteasome inhibitor (MG‐132) also downregulated the mRNA expression of AID. Moreover, curcumin (≤10 μmol/L) has suppressed H. pylori‐induced NF‐κB activation via inhibition of IKK activation and IκB degradation. Conclusion: Nonbactericidal concentrations of curcumin downregulated H. pylori‐induced AID expression in gastric epithelial cells, probably via the inhibition of NF‐κB pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori‐related gastric carcinogenesis.     

MiR-145 inhibits the migration and invasion of papillary thyroid carcinoma cells through NF-κB pathway regulation

Papillary thyroid carcinoma (PTC) is the most prevalent cancer in the endocrine system, and the number of patients diagnosed with PTC has been increasing rapidly in recent years. Previous studies have reported that miR-145 plays an important role in many kinds of cancers, but its function in PTC remains unclear. In this study, we found that compared to paracancerous tissues, the level of miR-145 expression was significantly downregulated in PTC tissues. When miR-145 is overexpressed, migration and invasion of PTC cells were suppressed in vitro. In addition, we found that miR-145 downregulated the nuclear factor-κB (NF-κB) pathway in PTC cells. Taken together, our data suggest that miR-145 functions as a tumor suppressor in PTC with the suppressive effect related to downregulation of the NF-κB pathway.     

Nuclear envelope organization in papillary thyroid carcinoma

Papillary thyroid carcinomas (PTCs) have characteristic nuclear shape changes compared to follicular-type thyroid epithelium. We tested the hypothesis that the altered nuclear shape results from altered distribution or expression of the major structural proteins of the nuclear envelope. Lamin A, lamin B1, lamin C, lamin B receptor (LBR), lamina-associated polypeptide 2 (LAP2), emerin, and nuclear pores were examined. PTC's with typical nuclear features by H&E were compared to non-neoplastic thyroid and follicular neoplasms using confocal microscopy, and semi-quantitative immunoblotting. Lamin A/C, lamin B1, LAP2, emerin, and nuclear pores all extend throughout the grooves and intranuclear inclusions of PTC. Their distribution and fluorescent intensity is not predictably altered relative to nuclear envelope irregularities. By immunoblotting, the abundance (per cell) and electrophoretic mobilities of lamin A, lamin B1, lamin C, emerin, and LAP2 proteins do not distinguish PTC, normal thyroid, or follicular neoplasms. These results do not support previously published predictions that lamin A/C expression is related to a loss of proliferative activity. At least three LAP2 isoforms are identified in normal and neoplastic thyroid. LBR is sparse or undetectable in all the thyroid samples. The results suggest that the irregular nuclear shape of PTC is not determined by these nuclear envelope structural proteins per se. We review the structure of the nuclear envelope, the major factors that determine nuclear shape, and the possible functional consequences of its alteration in PTC.     

Role of Dicer1 in thyroid cell proliferation and differentiation

DICER1 plays a central role in the biogenesis of microRNAs and it is important for normal development. Altered microRNA expression and DICER1 dysregulation have been described in several types of tumors, including thyroid carcinomas. Recently, our group identified a new somatic mutation (c.5438A>G; E1813G) within DICER1 gene of an unknown function. Herein, we show that DICER1 is overexpressed, at mRNA level, in a significant-relative number of papillary (70%) and anaplastic (42%) thyroid carcinoma samples, whereas is drastically downregulated in all the analyzed human thyroid carcinoma cell lines (TPC-1, BCPAP, FRO and 8505c) in comparison with normal thyroid tissue samples. Conversely, DICER1 is downregulated, at protein level, in PTC in comparison with normal thyroid tissues. Our data also reveals that DICER1 overexpression positively regulates thyroid cell proliferation, whereas its silencing impairs thyroid cell differentiation. The expression of DICER1 gene mutation (c.5438A>G; E1813G) negatively affects the microRNA machinery and cell proliferation as well as upregulates DICER1 protein levels of thyroid cells but has no impact on thyroid differentiation. In conclusion, DICER1 protein is downregulated in papillary thyroid carcinomas and affects thyroid proliferation and differentiation, while DICER1 gene mutation (c.5438A>G; E1813G) compromises the DICER1 wild-type-mediated microRNA processing and cell proliferation.     

The Role of Podoplanin in the Biology of Differentiated Thyroid Cancers

Podoplanin (PDPN), a mucin-type transmembrane glycoprotein specific to the lymphatic system is expressed in a variety of human cancers, and is regarded as a factor promoting tumor progression. The purpose of this study was to elucidate the molecular role of PDPN in the biology of thyroid cancer cells. PDPN expression was evaluated in primary thyroid carcinomas and thyroid carcinoma cell lines by RT-qPCR, Western blotting, IF and IHC. To examine the role of podoplanin in determining a cell''s malignant potential (cellular migration, invasion, proliferation, adhesion, motility, apoptosis), a thyroid cancer cell line with silenced PDPN expression was used. We observed that PDPN was solely expressed in the cancer cells of 40% of papillary thyroid carcinoma (PTC) tissues. Moreover, PDPN mRNA and protein were highly expressed in PTC-derived TPC1 and BcPAP cell lines but were not detected in follicular thyroid cancer derived cell lines. PDPN knock-down significantly decreased cellular invasion, and modestly reduced cell migration, while proliferation and adhesion were not affected. Our results demonstrate that PDPN mediates the invasive properties of cells derived from papillary thyroid carcinomas, suggesting that podoplanin might promote PTC progression.     

Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells

Background

The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches.

Methods

Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining.

Results

TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls.

Conclusion

A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam radiation or chemotherapy, with fewer side effects and improved quality of life.     

Down‐regulation of Notch‐1 and Jagged‐1 inhibits prostate cancer cell growth,migration and invasion,and induces apoptosis via inactivation of Akt,mTOR, and NF‐κB signaling pathways

Notch signaling is involved in a variety of cellular processes, such as cell fate specification, differentiation, proliferation, and survival. Notch‐1 over‐expression has been reported in prostate cancer metastases. Likewise, Notch ligand Jagged‐1 was found to be over‐expressed in metastatic prostate cancer compared to localized prostate cancer or benign prostatic tissues, suggesting the biological significance of Notch signaling in prostate cancer progression. However, the mechanistic role of Notch signaling and the consequence of its down‐regulation in prostate cancer have not been fully elucidated. Using multiple cellular and molecular approaches such as MTT assay, apoptosis assay, gene transfection, real‐time RT‐PCR, Western blotting, migration, invasion assay and ELISA, we found that down‐regulation of Notch‐1 or Jagged‐1 was mechanistically associated with inhibition of cell growth, migration, invasion and induction of apoptosis in prostate cancer cells, which was mediated via inactivation of Akt, mTOR, and NF‐κB signaling. Consistent with these results, we found that the down‐regulation of Notch‐1 or Jagged‐1 led to decreased expression and the activity of NF‐κB downstream genes such as MMP‐9, VEGF, and uPA, contributing to the inhibition of cell migration and invasion. Taken together, we conclude that the down‐regulation of Notch‐1 or Jagged‐1 mediated inhibition of cell growth, migration and invasion, and the induction of apoptosis was in part due to inactivation of Akt, mTOR, and NF‐κB signaling pathways. Our results further suggest that inactivation of Notch signaling pathways by innovative strategies could be a potential targeted approach for the treatment of metastatic prostate cancer. J. Cell. Biochem. 109: 726–736, 2010. © 2010 Wiley‐Liss, Inc.     

Overexpression of TRIM26 suppresses the proliferation,metastasis, and glycolysis in papillary thyroid carcinoma cells

Papillary thyroid carcinoma (PTC) is the common subtype of thyroid cancer, which is a common endocrine malignancy. Tripartite motif 26 (TRIM26) has been found to act as a tumor suppressor in several cancers. However, the functional roles of TRIM26 in PTC remain unknown. In this study, we examined the TRIM26 expression in PTC and evaluated the effects of TRIM26 on proliferation, metastasis, and glycolysis in PTC cells. The results proved that TRIM26 was significantly downregulated in PTC tissues and cell lines. TRIM26 overexpression inhibited cell proliferation, migration, and invasion in PTC cells. TRIM26 overexpression also suppressed the epithelial-to-mesenchymal transition process. Besides, overexpression of TRIM26 caused significant decrease in glucose uptake and lactate production in PTC cells. Further investigations revealed that TRIM26 overexpression inhibited the activation of PI3K/Akt pathway. Treatment with an activator (740Y-P) of the PI3K/AKT pathway reversed the antitumor effects of TRIM26 on PTC cells. These findings provided evidence that TRIM26 acted as a tumor suppressor in PTC.