Progression Of Thyroid Carcinoma Research Articles

PLS3 promotes papillary thyroid carcinoma progression by activating the Notch signaling pathway.

Thyroid cancer is the most common endocrine malignancy worldwide. Although significant progress has been made in understanding the genetic and molecular alterations that drive thyroid cancer, the mechanisms underlying thyroid tumor progression remain unclear. In this study, we explored the involvement of Plastin-3 (PLS3) in the progression of papillary thyroid cancer and elucidated the underlying molecular mechanisms. We first analyzed clinical samples from papillary thyroid cancer patients and found that PLS3 expression was significantly upregulated in tumor tissues compared to adjacent normal tissues. Moreover, high PLS3 expression was associated with advanced tumor stage and poor prognosis. Further in vitro and in vivo experiments showed that PLS3 could promote the proliferation, migration, and invasive behavior of papillary thyroid cancer cells, while PLS3 knockdown suppressed these processes. Mechanistically, we found that PLS3 promoted papillary thyroid cancer progression by activating the Notch signaling pathway. Specifically, PLS3 upregulated the expression of Notch receptors (Notch1) and downstream target gene (Hes1) in papillary thyroid cancer cells. In summary, our findings collectively indicate that PLS3 plays a pivotal role in driving the progression of papillary thyroid cancer and holds promise as a viable therapeutic target for the treatment of this disease.

Statement of Retraction: Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression

This article refers to:RETRACTED ARTICLE: Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression

MicroRNA-130a-3p impedes the progression of papillary thyroid carcinoma through downregulation of KPNB1 by targeting PSME3.

Papillary thyroid carcinoma (PTC) is the main type of thyroid cancer (THCA). Despite the good prognosis, some PTC patients may deteriorate into more aggressive disease, leading to poor survival. Our study aimed to explore the role of microRNA (miR)-130a-3p in regulating PTC. After transfection with miR-130a-3p-mimic, OE-PSME3, or miR-130a-3p-mimic + OE-KPNB1 in PTC cells (TPC-1), CCK-8, Transwell, scratch, and flow cytometry experiments were performed to analyze TPC-1 cell proliferation, invasion, migration, and apoptosis. Western blotting was used to detect proliferation or invasion-related protein markers (PCNA, E-cadherin, and N-cadherin). The RNA22 database, dual-luciferase reporter assay, and RNA pull-down assay were applied for the prediction and verification of the binding site between miR-130a-3p and PSME3. Pan-cancer software identified a positive correlation between PSME3 and KPNB1 in THCA. Co-immunoprecipitation was utilized to verify the interaction of PSME3 with KPNB1. Nude mice were transplanted with TPC-1 cells overexpressing miR-130a-3p. The tumors were isolated for detection of the expression of miR-130a-3p, PSME3, KPNB1, Ki-67, and CD31. miR-130a-3p was lowly expressed in PTC cell lines. Upregulation of miR-130a-3p repressed the expression of PSME3 and KPNB1 and reduced the malignancy of TPC-1 cells in vitro, shown by inhibited cell proliferation, invasion, migration, and the expression of PCNA and N-cadherin. Also, overexpressed miR-130a-3p inhibited the growth of xenograft tumors in nude mice. miR-130a-3p bound to PSME3 which interacted with KPNB1. miR-130a-3p impedes the progression of PTC by downregulating PSME3/KPNB1.

Circ_0003747 promotes thyroid cancer progression by sponging miR-338-3p to upregulate PLCD3 expression

ABSTRACT The circular RNAs (circRNAs) involved in competitive endogenous RNA (ceRNA) mechanism are critical modulators affecting pathogenesis of thyroid carcinoma (TC). The study’s goal was to investigate the effects of circ 0003747 on the biological progression of papillary thyroid cancer (PTC). Normal thyroid cells Nthy-ori3–1 and TC derived cell lines were used in our study. Sanger sequencing and RNase R treatment were utilized for validating the circular structure of circ_0003747. In our work, circ_0003747 was found to be highly expressed in TC cells. Circ_0003747 knockdown reduced TC cell viability, proliferation, migration, and invasion while increasing cell apoptosis. Circ_0003747 targeted and negatively regulated miR-338-3p expression. Besides, miR-338-3p interacted with PLCD3 to repress its expression. Overexpression of miR-338-3p inhibited TC cell progression, and PLCD3 reversed these effects. Furthermore, PLCD3 overexpression reversed the effects of circ_0003747 knockdown on TC cells. Additionally, the knockdown of circ_0003747 remarkably suppressed tumour size and growth, restrained PLCD3 expression and promoted miR-338-3p expression in nude mice. In conclusion, circ_0003747 facilitated the biological progression of TC by modulating the miR-338-3p/PLCD3 axis, and it may be a new target for TC treatment. Abbreviations: TC: Thyroid carcinoma; PTC: Papillary thyroid carcinoma; CircRNAs: Circular RNAs; MiRNA: MicroRNA; EMT: Epithelial-mesenchymal transition; HCC: Hepatocellular carcinoma; PLCD3: Phospholipase C Delta 3; CeRNA: Competitive endogenous RNA

Knockdown of Programmed Death 1 Inhibited Progression of Papillary Thyroid Carcinoma in Mice.

PD-L1 and PD1 mainly focused on melanoma, lung cancer and other tumors, while the related studies on early lymph node metastasis of papillary thyroid carcinoma were rarely reported. For elucidating the role of programmed death 1 (PD1)/programmed death ligand 1 (PD-L1) pathway in tumor growth of papillary thyroid carcinoma (PTC). Human thyroid cancer cell line and human normal thyroid cell line were obtained and transfected with si-PD1 or pCMV3-PD1 for the construction of PD1 knockdown or overexpression models. BALB/c mice were purchased for in vivo studies. Nivolumab was implemented for in vivo inhibition of PD1. Western blotting was performed for determining protein expression, while RTqPCR was used to measure relative mRNA levels. The PD1 and PD-L1 levels were both significantly upregulated in PTC mice, while the knockdown of PD1 downregulated both PD1 and PD-L1 levels. Protein expression of VEGF and FGF2 was increased in PTC mice, while si-PD1 decreased their expression. Silencing of PD1 using si-PD1 and nivolumab both inhibited tumor growth in PTC mice. Suppressing PD1/PD-L1 pathway significantly contributed to the tumor regression of PTC in mice.

FOXA2 suppresses PKM2 transcription and affects the Wnt/β-catenin activity to block aerobic glycolysis in thyroid carcinoma.

Aerobic glycolysis is critical for the energy metabolism of cancer cells. This study focuses on the regulation of forkhead box A2 (FOXA2) on pyruvate kinase M2 (PKM2) and their effects on the glycolytic activity and malignant phenotype of thyroid carcinoma (THCA) cells. By analysing four Gene Expression Omnibus datasets and querying bioinformatics systems, we obtained FOXA2 as a poorly expressed transcription factor in THCA. Later, we validated decreased mRNA and protein levels of FOXA2 in THCA cells by quantitative polymerase chain reaction and western blot assays. FOXA2 upregulation in THCA cells suppressed the glucose uptake and lactate production, and it reduced the extracellular acidification rate, but increased the oxygen consumption rate of cells. Meanwhile, the FOXA2 overexpression blocked the proliferation and mobility, and the tumourigenic activity of cancer cells. The chromatin immunoprecipitation and luciferase assays showed that FOXA2 bound to PKM2 promoter and suppressed the transcription of PKM2, which was highly expressed in THCA cells. Further upregulation of PKM2 elevated the β-catenin, c-Myc and cyclin D1 levels and restored the glycolytic activity as well as the malignant properties of cancer cells. Collectively, this work reveals that FOXA2 suppresses aerobic glycolysis and progression of THCA by blocking PKM2 transcription and inactivating the Wnt/β-catenin pathway.

LncRNA IGF2‐AS regulates miR‐500a‐3p/PPP4R1/p‐VEGFR2 signalling pathway to promote thyroid carcinoma progression and tubulogenesis

lncRNA IGF2‐AS regulates miR‐500a‐3p/PPP4R1/p‐VEGFR2 signalling pathway to promote thyroid carcinoma progression and tubulogenesis

Recapitulating thyroid cancer histotypes through engineering embryonic stem cells

Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAFV600E or NRASQ61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53R248Q generate undifferentiated TCs. Of note, TCs arise by engineering TPCs, whereas mature thyrocytes have a very limited tumorigenic capacity. The same mutations result in teratocarcinomas when delivered in early differentiating hESCs. Tissue Inhibitor of Metalloproteinase 1 (TIMP1)/Matrix metallopeptidase 9 (MMP9)/Cluster of differentiation 44 (CD44) ternary complex, in cooperation with Kisspeptin receptor (KISS1R), is involved in TC initiation and progression. Increasing radioiodine uptake, KISS1R and TIMP1 targeting may represent a therapeutic adjuvant option for undifferentiated TCs.

Expression of HIF-1α/PKM2 axis correlates to biological and clinical significance in papillary thyroid carcinoma.

hypoxia inducible factor-1α (HIF-1α) and pyruvate kinase M2 (PKM2) are 2 key metabolic regulatory proteins, they could engage in a positive feedback loop and drive cancer growth by enhancing glycolysis. This study aimed to investigate the expression of HIF-1α and PKM2 in papillary thyroid carcinoma (PTC) and its correlation with the patients clinicopathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 60 patients were collected. The expression levels of HIF-1α and PKM2 in PTC tissues were examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between HIF-1α and PKM2 expressions and the clinical pathological features of PTC. The results showed that the positive expressions of HIF-1α, PKM2, and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all significantly higher in PTC than those in normal thyroid follicular epithelium, and a positive correlation was found between HIF-1α and PKM2 in PTC. Further analysis showed that in PTC, the positive expression of HIF-1α and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were significantly associated with bigger tumor size, moreover, the positive expressions of HIF-1α, PKM2 and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all correlated with capsular invasion and lymph node metastasis, while they were all not correlated with gender, sex and multicentricity of tumor. This study identified HIF-1a/PKM2 axis as potential molecular marker for predicting the invasion and progression of papillary thyroid carcinoma.

Overexpression of the pro-protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling.

Furin belongs to the pro-protein convertases (PCs) family and its aberrant expression has been documented in various types of cancers; however, its role in thyroid cancer remains unclear. We investigated the expression of furin in a large cohort of Middle Eastern papillary thyroid carcinoma (PTC) patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. Furin overexpression was observed in 44.6% of all PTC cases and was significantly associated with aggressive clinicopathological parameters and poor outcomes. We show that the knockdown of FURIN suppresses tumor growth, proliferation, migration, invasion, spheroid growth, and progression of epithelial-to-mesenchymal transition (EMT) in B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutant cells, whereas its overexpression in BRAF wild-type PTC cell lines reversed the effect. FURIN knockdown in the BRAF mutant cell line led to reduced tumor growth and increased apoptosis. Mechanistically, FURIN knockdown led to MEK/ERK pathway suppression in BRAF mutant cells, although inhibition of MEK did not affect furin expression, which suggests that furin acts through the MEK/ERK pathway. Furthermore, our study revealed the synergistic antitumor effect of furin depletion and anti-MEK inhibitor treatment. Overall, these results indicate that furin is an important prognostic marker in Middle Eastern PTC and that it plays a crucial role in BRAF-associated MAP/ERK pathway activation and tumorigenesis. Furin inhibition could be a potential therapeutic target for aggressive PTC.

STRA6 regulates tumor immune microenvironment and is a prognostic marker in BRAF-mutant papillary thyroid carcinoma.

BRAF mutation is one of the most common genetic alterations contributing to the initiation and progression of papillary thyroid carcinoma (PTC). However, the prognostic value of BRAF mutation for PTC is limited. Novel markers are needed to identify BRAF-mutant patients with poor prognosis. Transcriptional expression data were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Pathway enrichment was performed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA). Protein-protein interaction networks were predicted by the GeneMANIA. The correlation between STRA6 expression and immune infiltration was analyzed by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB). Immunohistochemistry was used to detect the STRA6 protein expression level of PTC. Infiltration of regulatory T cells (Tregs) and CD8+ T cells in tumor samples were analyzed by fluorescent multiplex immunohistochemistry. In BRAF-mutant PTC, STRA6 was extremely upregulated and predicted unfavorable survival, which was an independent risk factor for increased mortality risk. Bioinformatic analyses indicated that STRA6 might activate the MAPK pathway synergistically with BRAFV600E. The expression of STRA6 was associated with immune infiltrates and T cell exhaustion. Fluorescent multiplex immunohistochemistry showed that STRA6 increased Tregs abundance and decreased CD8+ T cells infiltration in PTC. Moreover, STRA6 promoted epithelial-mesenchymal transition via increased cancer-associated fibroblasts infiltration. Our study demonstrates STRA6 may serve as a prognostic marker for BRAF-mutated PTC, which may drive thyroid carcinogenesis via activation of oncogenic pathway and regulation of tumor immunosuppressive microenvironment.

STRA6 Promotes Thyroid Carcinoma Progression via Activation of the ILK/AKT/mTOR Axis in Cells and Female Nude Mice.

Metastasis has emerged to be an important cause for poor prognosis of thyroid carcinoma (TC) and its molecular mechanisms are not fully understood. STRA6 is a multifunctional membrane protein widely expressed in embryonic and adult tissues. The function and mechanism of STRA6 in TC remain elusive. We aimed to explore the role of STRA6 in TC progression and provide a therapeutic target for TC. The expression and clinicopathological relevance of STRA6 were explored in TC. Stable STRA6-knockdown TC cells were established and used to determine the biological function of STRA6 in vitro and in vivo. RNA sequencing and co-immunoprecipitation were performed to unveil the molecular mechanism of STRA6 in TC progression. The potential of STRA6 as a therapeutic target was evaluated by lipid nanoparticles (LNPs) containing siRNA. STRA6 was upregulated in TC and correlated with aggressive clinicopathological features, including extrathyroidal extension and lymph node metastasis, which contributed to the poor prognosis of TC. STRA6 facilitated TC progression by enhancing proliferation and metastasis in vitro and in vivo. Mechanistically, STRA6 could interact with integrin-linked kinase (ILK) and subsequently activate the protein kinase B/mechanistic target of rapamycin (AKT/mTOR) signaling pathway. We further unveiled that STRA6 reprogrammed lipid metabolism through SREBP1, which was crucial for the metastasis of TC. Moreover, STRA6 siRNA delivered by LNPs significantly inhibited cell growth in xenograft tumor models. Our study demonstrates the critical roles of STRA6 contributing to TC progression via the ILK/AKT/mTOR axis, which may provide a novel prognostic marker as well as a promising therapeutic target for aggressive TC.

Retracted: miR-196a-2 Promotes Malignant Progression of Thyroid Carcinoma by Targeting NRXN1.

[This retracts the article DOI: 10.1155/2021/4856820.].

Aurora kinase a promotes the progression of papillary thyroid carcinoma by activating the mTORC2-AKT signalling pathway

BackgroundTreatment failure is the main cause of death from papillary thyroid carcinoma (PTC). It is urgent to look for new intervention targets and to develop new therapies for treating PTC. Aurora-A kinase (AURKA) functionally regulates cell mitosis and is closely related to the occurrence and development of a variety of tumours. However, the expression and potential functions of AURKA in PTC remain largely elusive.ResultsClinicopathologically, AURKA is highly expressed in PTC tissues compared to normal tissues and is correlated with lymph node metastasis, TNM stage and patient prognosis. Biologically, AURKA functions as an oncoprotein to promote the proliferation and migration of PTC cells. Mechanistically, AURKA directly binds to SIN1 and compromises CUL4B-based E3 ligase-mediated ubiquitination and subsequent degradation of SIN1, leading to hyperactivation of the mTORC2-AKT pathway in PTC cells.ConclusionsWe found that AURKA plays critical roles in regulating the progression of PTC by activating the mTORC2-AKT pathway, highlighting the potential of targeting AURKA to treat PTC.

Effect of GATAD1 regulating the SRRM2 gene on recurrence of thyroid tumor and its molecular mechanism.

Thyroid blood vessels and nerves are rich, and their anatomical and physiological structures are complex. Surgery often fails to eradicate the tumor, which has a serious negative impact on the surgical outcomes and patient prognosis. Therefore, it is important to accurately predict the recurrence rate of thyroid cancer. Based on bioinformatics analysis, the highly expressed transcription factors and differential genes in thyroid carcinoma (THCA) were obtained. Kaplan-Meier survival analysis was used to analyze the clinical effects of GATAD1 as well as SRRM2 on the recurrence of THCA patients. The effect of GATAD1 on SRRM2 expression was explored using cell experiments. Other experiments were conducted to reveal the interaction between SRRM2 and GATAD1 and their functions in THCA progression, such as cell proliferation and cell cycle. GATAD1 was overexpressed in recurrent THCA tissue compared with that in adjacent normal tissue. GATAD1 and SRRM2 were identified as the key risk factors for THCA recurrence as well as survival. Knockdown of GATAD1 and SRRM2 can inhibit THCA cell proliferation and arrest THCA cells in the G1 phase. Inhibiting GATAD1 decreased SRRM2 expression in THCA cells, whereas overexpressing GATAD1 had the opposite result. SRRM2 knockdown eliminated GATAD1-induced proliferation of THCA cells in vitro, indicating that GATAD1-induced THCA cell proliferation was dependent on increased SRRM2 expression. We identified GATAD1 as an underlying diagnostic biomarker in THCA recurrence patients. The GATAD1-SRRM2 axis mediates human THCA recurrence progression and is an underlying target for THCA treatment.

Correction for: Long non-coding RNA DLEUI promotes papillary thyroid carcinoma progression by sponging miR-421 and increasing ROCK1 expression.

Correction for: Long non-coding RNA DLEUI promotes papillary thyroid carcinoma progression by sponging miR-421 and increasing ROCK1 expression.

SYTL5 Promotes Papillary Thyroid Carcinoma Progression by Enhancing Activation of the NF-κB Signaling Pathway.

The function and mechanism of SYTL5 in papillary thyroid carcinoma (PTC) are still unclear. In this research, we found that SYTL5 was significantly overexpressed in PTC tissues compared with normal thyroid tissues. SYTL5 downregulation significantly weakened the proliferative, migratory, and invasive abilities of PTC cells. In addition, upregulated SYTL5 could promote cancer progression by activating the NF-κB signaling pathway. RAC1b expression is positively associated with SYTL5, and overexpressed RAC1b abrogated the antitumor effect after SYTL5 inhibition. In conclusion, our findings identify the oncogenic role of SYTL5 in PTC by activation of the NF-κB signaling pathway, thus facilitating PTC development and progression.

NKD2 is correlated with the occurrence, progression and prognosis of thyroid carcinoma

BackgroundThyroid carcinoma (THCA) is the most prevalent type of tumor in endocrine system. NKD2 has been increasingly evidenced to play crucial roles in many cancers, except for THCA. We herein aimed to explore the potential role of NKD2 in THCA.MethodsTotally 502 THCA patient data were downloaded from TCGA (The Cancer Genome Atlas) database. Overall survival was estimated by Kaplan–Meier method. Gene set enrichment analysis was conducted to obtain significant functional pathways. Wilcoxon rank sum test was used to determine the NKD2 expression differences among various groups. The NKD2 expression was validated in cell lines and tissue microarray.ResultsSignificantly higher NKD2 expression was observed in THCA samples compared with adjacent samples, which were successfully verified in cell lines and tissue microarray. Moreover, NKD2 expression gradually elevated along with the increase of TNM Stage, and NKD2 expression was significantly higher in elder THCA patients compared with young patients. NKD2 highly expressed THCA patients had worse prognosis compared with NKD2 low-expressed patients. Furthermore, 53 pathways were significantly activated in the high NKD2 expression patients compared with low NKD2 expression THCA patients.ConclusionsIn summary, high NKD2 expression was probably related to the progression and poor prognosis of THCA. NKD2 is a promising prognostic biomarker and pathogenic target of THCA.

Thyroid carcinoma-featured telomerase activation and telomere maintenance: Biology and translational/clinical significance.

Telomerase is a ribonucleoprotein complex consisting of a catalytic component telomerase reverse transcriptase (TERT), internal RNA template and other co-factors, and its essential function is to synthesize telomeric DNA, repetitive TTAGGG sequences at the termini of linear chromosomes. Telomerase is silent in normal human follicular thyroid cells, primarily due to the TERT gene being tightly repressed. During the development and progression of thyroid carcinomas (TCs), TERT induction and telomerase activation is in general required to maintain telomere length, thereby conferring TC cells with immortal and aggressive phenotypes. The genomic alterations of the TERT loci including TERT promoter's gain-of-function mutations, copy number gain, fusion and rearrangements, have recently been identified in TCs as mechanisms to induce TERT expression and to activate telomerase. Importantly, numerous studies have consistently shown that TERT promoter mutations and TERT expression occur in all TC subtypes, and are robustly associated with TC malignancy, aggressiveness, treatment failure and poor outcomes. Therefore, the assessment of TERT promoter mutations and TERT expression is highly valuable in TC diagnostics, prognosis, treatment decision, and follow-up design. In addition, the TERT promoter is frequently hypermethylated in TC cells and tumors, which is required to activate TERT transcription and telomerase. Dysregulation of other components in the telomerase complex similarly upregulate telomerase. Moreover, shortened telomeres lead to altered gene expression and metabolism, thereby actively promoting TC aggressiveness. Here we summarize recent findings in TCs to provide the landscape of TC-featured telomere/telomerase biology and discuss underlying implications in TC precision medicine. Mechanistic insights into telomerase activation and TERT induction in TCs are important both biologically and clinically. The TERT gene aberration and expression-based molecular classification of TCs is proposed, and for such a purpose, the standardization of the assay and evaluation system is required. Moreover, the TERT-based system and 2022 WHO TC classification may be combined to improve TC care.

Circ_0002111/miR-134-5p/FSTL1 signal axis regulates tumor progression and glycolytic metabolism in papillary thyroid carcinoma cells.

Circular RNAs (circRNAs) have essential roles in the malignant progression of papillary thyroid carcinoma (PTC). Circ_0002111 was reported to facilitate cell proliferation and invasion abilities in PTC. This study was performed to explore the regulatory mechanism of circ_0002111 in PTC progression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used for the level detection of circ_0002111, microRNA-134-5p (miR-134-5p) and Follistatin Like 1 (FSTL1). Cell proliferation was assessed by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, EdU assay and colony formation assay. Cell migration ability was determined by transwell assay. Glycolysis was analyzed by extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose consumption and lactate production. The protein quantification was performed through western blot. Xenograft tumor assay was used for the functional analysis of circ_0002111 in vivo. The target interaction was confirmed by dual-luciferase reporter assay and RNA pull-down assay. The significant upregulation of circ_0002111 was detected in PTC samples and cells. PTC cell proliferation, migration and glycolytic metabolism were suppressed after circ_0002111 downregulation. PTC tumorigenesis in vivo was also inhibited by circ_0002111 knockdown. In addition, circ_0002111 could target miR-134-5p and si-circ_0002111#1-induced inhibition of PTC progression was relieved by miR-134-5p expression downregulation. Furthermore, FSTL1 was a target gene for miR-134-5p and miR-134-5p served as a tumor repressor in PTC by targeting FSTL1. Moreover, circ_0002111 could increase the FSTL1 level via sponging miR-134-5p. All results indicated that circ_0002111 promoted the malignant behaviors of PTC cells partly by regulating the miR-134-5p/FSTL1 molecular network.