Papillary Thyroid Cancer Cell Invasion Research Articles

SYVN1 modulates papillary thyroid carcinoma progression by destabilizing HMGB1

E3 ubiquitin ligase synoviolin (SYVN1) has been reported to participate in many human cancers. This study aimed to investigate SYVN1’s roles and molecular pathways in papillary thyroid cancer (PTC). The functions of SYVN1 in PTC were further analyzed using gain- and loss-of-function methods and numerous investigations in cellular function and molecular biology. The findings demonstrated that the overexpression of SYVN1 markedly suppressed the proliferation, migration, and invasion of PTC cell lines (NPA87 and TPC-1). We found that SYVN1 interacted with HMGB1 and promoted its ubiquitination and degradation. In addition, SYVN1 effectively impairs cell proliferation, migration, invasion, and the formation of tumor xenografts in mice models. However, this effect may be partly reversed by overexpressing HMGB1. Thus, SYVN1 may inhibit the proliferation, migration, and invasion of PTC cells by disrupting HMGB1. Consequently, SYVN1 might be considered a promising therapeutic target for PTC.

Functional analysis of ESM1 by shRNA-mediated knockdown of its expression in papillary thyroid cancer cells.

Endothelial specific molecule-1 (ESM1) is implicated as an oncogene in multiple human cancers. However, the function of ESM1 in papillary thyroid cancer (PTC) is not well understood. The current study aimed to investigate the effect of ESM1 on the growth, migration, and invasion of PTC to provide a novel perspective for PTC treatment. The expression levels of ESM1 in PTC tissues form 53 tumor tissue samples and 59 matching adjacent normal tissue samples were detected by immunohistochemical analysis. Knockdown of ESM1 expression in TPC-1 and SW579 cell lines was established to investigate its role in PTC. Moreover, cell proliferation, apoptosis, wound healing, and transwell assays were conducted in vitro to assess cell proliferation, migration and invasion. The findings revealed that ESM1 expression was significantly higher in PTC tissues than that found in paraneoplastic tissues (P<0.0001). Knockdown of ESM1 expression inhibited the proliferation, migration, and invasion of TPC-1 and SW579 cells in vitro. Compared with the control group, the mRNA and protein levels of ESM1 in PTC cells were significantly reduced following knockdown of its expression (P<0.01). In addition, ESM1-knockdown cells indicated decreased proliferation and decreased migratory and invasive activities (P<0.01, P<0.01, P<0.001, respectively). ESM1 was identified as a major gene in the occurrence and progression of PTC, which could increase the proliferation, migration, and invasion of PTC cells. It may be a promising diagnostic and therapeutic target gene.

FLNA overexpression promotes papillary thyroid cancer aggression via the FAK/AKT signaling pathway.

Filamin A (FLNA) is a member of the filamin family and has been found to be critical for the progression of several cancers. However, its biological function in papillary thyroid cancer (PTC) remains largely unexplored. Data from The Cancer Genome Atlas (TCGA) databases were utilized to analyze the FLNA expression level and its influence on the clinical implications of patients with PTC. Gene Expression Omnibus (GEO) and qRT-PCR was used to verify the expression levels of FLNA in PTC. Kaplan-Meier survival analysis was conducted to evaluate the prognostic value of FLNA in PTC. Transwell assays and wound healing were performed to examine the biological function of FLNA knockdown in PTC cells. Gene set enrichment analysis (GSEA) and Western blotting were conducted to investigate the potential mechanisms underlying the role of FLNA in PTC progression. In addition, the relationship between FLNA expression and the tumor immune microenvironment (TME) in PTC was explored. FLNA was significantly upregulated in PTC tissues. High expression levels of FLNA was correlated with advanced TNM stage, T stage, and N stage, as well as poor disease-free interval (DFI) and progression-free interval (PFI) time in PTC patients. Moreover, we found that FLNA knockdown inhibited the migration and invasion of PTC cells. Mechanistically, FLNA knockdown inhibited epithelial-mesenchymal transition (EMT) in PTC and affected the activation of the FAK/AKT signaling pathway. In addition, FLNA expression was associated with TME in PTC. FLNA may be regarded as a new therapeutic target for PTC patients.

BCL9 is a Risk Factor of Neck Lymph Nodes Metastasis and Correlated with Immune Cell Infiltration in Papillary Thyroid Carcinoma.

B-cell lymphoma 9 (BCL9), a key transcription co-activator of the Wnt pathway, contributed to tumor progression and metastasis in various tumors, whereas, the role of BCL9 in papillary thyroid cancer (PTC) has not been investigated. We acquired PTC gene expression data from The Cancer Genome Atlas (TCGA) database. Fifty-nine PTC tissues were applied to validate the clinical significance of BCL9. Cell experiments were applied to investigate the role of BCL9. Bioinformatics analysis was employed to investigate the biological functions of BCL9. We found that BCL9 was higher expressed (P < 0.05) and an independent risk factor for lymph node metastasis (OR = 3.770, P = 0.025), as well as associated with poorer progression-free survival (PFS) (P = 0.049) in PTC. BCL9 knockdown inhibited proliferation and invasion of PTC cells. BCL9 was positively associated with the key genes of Wnt/β-catenin and MAPK pathway by co-expression analysis. GO, KEGG and GSEA analysis showed BCL9 might participated in PPAR, cAMP, and focal adhesion pathway. CIBERSORT analysis found BCL9 was negatively associated with CD8+ T cells and NK cell infiltration and positively with PD-L1 expression. Therefore, BCL9 was associated with lymph node metastasis and shorter PFS of PTC, due to promotion of PTC cell proliferation and invasion, activation of Wnt/β-catenin and MAPK pathway, inhibition of CD8+ T and NK cell infiltration, and promotion of PD-L1 expression.

LncRNA HCG22 regulated cell growth and metastasis of papillary thyroid cancer via negatively modulating miR-425-5p.

Papillary thyroid cancer (PTC) is a common malignant tumour in the endocrine system with increasing incidence. LncRNA HCG22 (HCG22) was noticed to be dysregulated in PTC, but its specific function and mechanism remain unknown. The function of HCG22 and its underlying molecular mechanism was investigated to evaluate its potential as a biomarker for PTC. The expression of HCG22 was detected in PTC cells (TPC-1, SNU790, GLAG-66, and BCPAP) and normal thyroid cells (Nthy-ori) using real time quantative polymerase chain reaction (RT-qPCR). HCG22 and miR-425-5p were regulated by cell transfection. The cell proliferation and metastasis were assessed by CCK8 and Transwell assay. HCG22 was upregulated in PTC cells, of which the knockdown suppressed the proliferation, migration, and invasion of PTC cells. miR-425-5p was downregulated in PTC cells, which was negatively regulated by HCG22. Silencing miR-425-5p could reverse the inhibitory effect of HCG22 knockdown on the cellular processes of PTC. HCG22 served as a tumour promoter in PTC cells, which regulated cell proliferation and metastasis via negatively regulating miR-425-5p.

AEBP1 promotes papillary thyroid cancer progression by activating BMP4 signaling

Papillary thyroid cancer (PTC) is the most prevalent endocrine cancer worldwide. Approximately 30 % of PTC patients will progress into the advanced or metastatic stage and have a relatively poor prognosis. It is well known that epithelial-mesenchymal transition (EMT) plays a pivotal role in thyroid cancer metastasis, resistance to therapy, and recurrence. Clarifying the molecular mechanisms of EMT in PTC progression will help develop the targeted therapy of PTC. The aberrant expression of some transcription factors (TFs) participated in many pathological processes of cancers including EMT. In this study, by performing bioinformatics analysis, adipocyte enhancer-binding protein 1 (AEBP1) was screened as a pivotal TF that promoted EMT and tumor progression in PTC. In vitro experiments indicated that knockout of AEBP1 can inhibit the growth and invasion of PTC cells and reduce the expression of EMT markers including N-cadherin, TWIST1, and ZEB2. In the xenograft model, knockout of AEBP1 inhibited the growth and lung metastasis of PTC cells. By performing RNA-sequencing, dual-luciferase reporter assay, and chromatin immunoprecipitation assay, Bone morphogenetic protein 4 (BMP4) was identified as a downstream target of AEBP1. Over-expression of BMP4 can rescue the inhibitory effects of AEBP1 knockout on the growth, invasion, and EMT phenotype of PTC cells. In conclusion, these findings demonstrated that AEBP1 plays a critical role in PTC progression by regulating BMP4 expression and the AEBP1-BMP4 axis may present novel therapeutic targets for PTC treatment.

TRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming

tRFs and tiRNAs (tRNA-derived fragments) are an emerging class of small noncoding RNAs produced by the precise shearing of tRNAs in response to specific stimuli. They have been reported to regulate the pathological processes of numerous human cancers. However, the biofunction of tRFs and tiRNAs in the development and progression of papillary thyroid cancer (PTC) has not been reported yet. In this study, we aimed to explore the biological roles of tRFs and tiRNAs in PTC and discovered that a novel 5′tRNA-derived fragment called tRF-1:30-Gly-CCC-3 (tRF-30) was markedly down-regulated in PTC tissues and cell lines. Functionally, tRF-30 inhibited the proliferation and invasion of PTC cells. Mechanistically, tRF-30 directly bound to the biotin-dependent enzyme pyruvate carboxylase (PC), downregulated its protein level, interfered with the TCA cycle intermediate anaplerosis, and thus affected metabolic reprogramming and PTC progression. These findings revealed a novel regulatory mechanism for tRFs and a potential therapeutic target for PTC.

KMT2D Regulates the NCOA6/THRB Signal Axis through Epigenetic Modification to Promote the Migration and Invasion of Papillary Thyroid Cancer.

The histone lysine methyltransferase Histone-lysine N-methytransferase 2D (KMT2D) is a common mutated gene in a variety of cancers, including papillary thyroid cancer (PTC). However, the mechanism of KMT2D on the progression of PTC remains unclear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to evaluate KMT2D expression between human normal cell (Nthy-ori 3-1) and PTC cells (TPC1, IHH-4 and BCPAP). Proliferation, migration and invasion of TPC1, IHH-4 and BCPAP were assessed by Cell Counting Kit-8 (CCK-8), Wound-healing assay and Transwell assay. The mechanism of KMT2D on thyroid papillary cancer was explored with Chromatin immunoprecipitation assay (ChIP), qRT-PCR and Western blotting. The expression of KMT2D in PTC cells was significantly increased. Downregulation of KMT2D significantly decreased the proliferation, migration and invasion of PTC cells, which was correlated with decreased expression levels of H3K4me2, H3K9me2, NCOA6 and THRB. Meanwhile, ChIP assay demonstrated that KMT2D was associated with NCOA6. Study have shown that the downregulation of KMT2D reduces proliferation, migration and invasion of thyroid papillary carcinoma cells through epigenetic modification of NCOA6/THRB signal axis. These results provide a new insight into the role of KMT2D in migration and invasion of PTC.

Exosomal miR-655-3p inhibits growth, and invasion and macrophage M2 polarization through targeting CXCR4 in papillary thyroid carcinoma

Papillary thyroid cancer (PTC) is an endocrine malignancy whose incidence has increased rapidly worldwide. Exosome-miR-655-3p was down-regulated in patients with PTC. However, the effect and molecular mechanism of exosome-miR-655-3p in PTC was indistinct until now. Our study found that exosome-miR-655-3p was decreased in serum of PTC patients. Overexpression of miR-655-3p with mimics significantly shrunk the cell viability, reduced the number of chemotactic and invasive PTC cells. Besides, the proportion of CD163 positive cells and the expression of markers of M2 subtype macrophages was markedly decreased when mononuclear macrophage THP-1 was cultured with exosomes of miR-655-3p mimics. Oppositely, the inhibitor of miR-655-3p exacerbated growth, chemotaxis and invasion of PTC cells, and enhanced the M2 subtype macrophages. Structurally, miR-655-3p could target the 3' untranslated region (3'UTR) of CXCR4 and restrict the expression of CXCR4. In Xenograft tumor experiment, upregulated exosome-miR-655-3p effectively inhibited the growth of tumor and reduced the expression of CXCR4, Ki67 and CD163 in vivo. In summary, exosomal miR-655-3p inhibited growth, invasion and macrophage M2 polarization through targeting CXCR4 in papillary thyroid carcinoma. Regulating exosome-miR-655-3p/CXCR4 may be a potential treatment strategy for PTC.

Circular RNA VANGL1 Facilitates Migration and Invasion of Papillary Thyroid Cancer by Modulating the miR-194/ZEB1/EMT Axis.

Circular RNAs (circRNAs) are often aberrantly expressed in human tumors and also serve a critical regulatory role in papillary thyroid cancer (PTC). The aim of this study is to investigate the expression pattern and biological role of circVANGL1 in PTC. The results revealed that circVANGL1 was significantly upregulated in human PTC samples. In addition, high circVANGL1 expression was closely associated with adverse clinical parameters of PTC patients. Our in vitro experiments further indicated that the knockdown of circVANGL1 using siRNA obviously repressed migration, proliferation, EMT, and invasion of PTC cells, while opposite effects were induced by its overexpression. We further noted that circVANGL1 could interact with miR-194 directly in PTC, and serve as a ceRNA to regulate ZEB1 function. Moreover, miR-194 inhibition markedly abrogated the effects of circVANGL1 knockdown in PTC cells. Therefore, our results provide convincing evidence that circVANGL1 may exert oncogenic effects in PTC, partly via regulating the miR-194/ZEB1 axis.

MiR-200c promotes papillary thyroid cancer cell proliferation, migration, and invasion by downregulating PTEN

MiR-200c has been reported in several types of human cancer. Nevertheless, the expression profile and biological functions of miR-200c remain uncovered papillary thyroid cancer (PTC). The expression level of miR-200c was evaluated in PTC tissues using RT-qPCR. Survival analysis was performed in a cohort of 88 PTC patients. The effects of miR-200c on cell proliferation, migration, and invasion capacities were analyzed using CCK-8 and transwell assays. Target genes of miR-200c were assessed using luciferase reporter assay, RT-qPCR, Western blot and rescue experiments. MiR-200c was found to be upregulated in human PTC tissues and closely associated with pN stage and distant metastasis. High expression of miR-200c was associated with poor clinical prognosis in PTC patients. Whilst overexpression of miR-200c was demonstrated to promote the proliferation, migration, and invasion of PTC cells; knockdown of miR-200c showed an opposite inhibitory effect. Bioinformatics analysis and luciferase reporter assays confirmed that PTEN is a downstream target of miR-200c. Functional assays demonstrated that PTC cell proliferation, migration, and invasion were promoted by miR-200c via negative regulation of PTEN. Finally, overexpression of PTEN was shown to partially reverse the tumor promoting effect of miR-200c. In conclusion, this study indicates that miR-200c is a crucial prognostic biomarker of PTC, and that targeting of miR-200c/ PTEN axis may be of therapeutic significance in PTC patients.

Downregulation of miR-519d-3p is Associated with Poor Outcomes and Facilitates Tumor Progression in Papillary Thyroid Cancer by Regulating FOXQ1.

MicroRNA-519d-3p (miR-519d-3p) has emerged as a tumor suppressor in several human cancers. But whether miR-519d-3p is involved in papillary thyroid cancer (PTC) remains elusive. In this study, we investigated the potential relevance of miR-miR-519d-3p in PTC. A retrospective study of 119 PTCs was carried out. The RT-qPCR analysis was used to measure the expression of miR-519d-3p and FOXQ1 in PTC tissues and cells. Chi-square test, Kaplan-Meier curve analysis, and multivariate Cox regression analyses were performed to assess the clinical and prognostic value of miR-519d-3p in PTC. Then cellular experiments were used to explore its biological effects on PTC cells. Finally, the Pearson correlation coefficient, dual-luciferase reporter assay, and rescue experiments were used to analyze the association between miR-519d-3p and FOXQ1. miR-519d-3p was significantly downregulated in PTC tissues and cell lines. The decreased expression of miR-519d-3p was associated with reduced overall survival and progression-free survival of patients. The proliferative, migratory, and invasive abilities of cells were blocked or elevated after upregulation or downregulation of miR-519d-3p, while FOXQ1 reversed these cellular behaviors caused after upregulation or knockdown of miR-519d-3p. In conclusion, miR-519d-3p was downregulated in PTC and associated with OS and PFS of patients. MiR-519d-3p may be a tumor-inhibiting miRNA in PTC, and that miR-519d-3p/FOXQ1 axis mediated PTC tumor progression from cell proliferation, migration, and invasion in PTC cells.

Bone Marrow Mesenchymal Stem Cells (BMSCs) Induces Resistance to Papillary Thyroid Cancer by Activating Janus Kinase/Signal Transducer and Activator of Transcription 3(JAK/STAT3)

We aimed to explore the mechanism underlying bone marrow mesenchymal stem cells (BMSCs) interacting the drug resistance in papillary thyroid cancer (PTC). In this study, we cultivated and screened cisplatin-resistant PTC cells. The shRNA targeting STAT3 was cloned into the pLKO.1-TRC vector and the vector was transfected into the cancer cells. Afterwards, MTT, Transwell and flow cytometry assay were performed to detect the cell invasion, metastasis and apoptosis, while the expression of JAK pathway related proteins was analyzed through Western blot. Besides, MSCs obtained from mouse blood were co-cultured with treated cells. The cells were injected into mice to detect in vivo effect of STAT3 and BMSCs on tumor growth. Compared with intravenous injection of MSCs, subcutaneous injection more effectively induced resistance to cisplatin, oxaliplatin or carboplatin. Combined treatment of sh-STAT3 restored the sensitivity of tumor cells to chemotherapy. BMSCs injection reduced apoptosis of PTC cells, but hardly affected proliferation. Co-cultivation with BMSCs activated the PI3 K/Akt pathway in PTC cells and enhanced tumor growth. Transfection of shSTAT3 inactivated PI3 K/Akt pathway, promoted cell apoptosis and inhibit cell invasion. Co-culture with BMSCs promotes the malignant invasion of PTC cells through the activation of JAK/STAT3 and induces chemotherapy resistance of PTC cells.

Curcumin inhibits the viability, migration and invasion of papillary thyroid cancer cells by regulating the miR-301a-3p/STAT3 axis.

Thyroid cancer is one of the most common malignant tumors, and the mortality rate associated with thyroid cancer has been increasing annually. Curcumin has been reported to exert an antitumor effect on papillary thyroid cancer (PTC), and the identification of additional mechanisms underlying the anticancer effect of curcumin on PTC requires further investigation. The present study aimed to explore the effects of curcumin on the viability, migration and invasion of PTC cells. TPC-1 cells were incubated with different concentrations of curcumin, and then, cell viability, migration and invasion, and wound healing were examined by CCK-8, Transwell and wound healing assays, respectively. Subsequently, microRNA (miR)-301a-3p mimics, miR-301a-3p inhibitors and signal transducer and activator of transcription (STAT)3 overexpression vector were transfected into TPC-1 cells, and cell viability, migration, and invasion were reassessed in these transfected cells. Matrix metallopeptidase (MMP)-2, MMP-9, epithelial-mesenchymal transition (EMT)-related markers, and Janus kinase (JAK)/STAT signaling pathway components were assessed by western blot analysis. Curcumin significantly inhibited cell viability, migration and invasion and downregulated MMP-2, MMP-9 and EMT marker expression. Additionally, curcumin decreased STAT3 expression by upregulating miR-301a-3p expression, and the inhibition of miR-301a-3p and the overexpression of STAT3 reversed the effects of curcumin on cell viability, migration and invasion, and MMP-2, MMP-9 and EMT marker expression in TPC-1 cells. Furthermore, curcumin suppressed the JAK/STAT signaling pathway through the miR-301a-3p/STAT3 axis. The data of the present study indicated that curcumin could inhibit the viability, migration and invasion of TPC-1 cells by regulating the miR-301a-3p/STAT3 axis. These findings may provide a possible strategy for the clinical treatment of PTC.

Circ-PSD3 promoted proliferation and invasion of papillary thyroid cancer cells via regulating the miR-7-5p/METTL7B axis

Papillary thyroid cancer (PTC) is a common tumor malignancy of the endocrine system worldwide. Recently, circular RNAs (circRNAs) have been reported to participate in diverse pathological processes, especially in tumorigenesis. However, the functional role and mechanism of circRNA pleckstrin and Sec7 domain containing 3 (circ-PSD3) in PTC are still unclear. In this study, qRT-PCR results showed that circ-PSD3 was significantly upregulated in PTC tissues and cell lines. Meanwhile, circ-PSD3 overexpression was positively associated with larger tumor size, TNM stage, and lymph node metastasis. Knockdown of circ-PSD3 suppressed the proliferation and invasion of PTC cells. Besides, circ-PSD3 interacted with miR-7-5p to reduce its expression, and methyltransferase like 7B (METTL7B) was verified as a target gene of miR-7-5p. Functionally, inhibition of circ-PSD3 impeded PTC cell proliferation and invasion via targeting miR-7-5p to downregulate METTL7B expression. Taken together, silencing of circ-PSD3 hampered the proliferation and invasion of PTC cells via upregulating the inhibitory effect of miR-7-5p on METTL7B expression. Therefore, circ-PSD3 could be a potential diagnostic biomarker or molecular treatment target for PTC.

HYOU1 facilitates proliferation, invasion and glycolysis of papillary thyroid cancer via stabilizing LDHB mRNA.

HYOU1 is upregulated in many kinds of cancer cells, and its high expression is associated with tumour invasiveness and poor prognosis. However, the role of HYOU1 in papillary thyroid cancer (PTC) development and progression remains to be elucidated. Here, we reported that HYOU1 was highly expressed in human PTC and associated with poor prognosis. HYOU1 silencing suppressed the proliferation, migration and invasion of PTC cells. Mechanistic analyses showed that HYOU1 silencing promoted oxidative phosphorylation while inhibited aerobic glycolysis via downregulating LDHB at the posttranscriptional level. We further confirmed that the 3'UTR of LDHB mRNA is the indirect target of HYOU1 silencing and HYOU1 silencing increased miR‐375‐3p levels. While LDHB overexpression significantly suppressed the inhibitory effects of HYOU1 silencing on aerobic glycolysis, proliferation, migration and invasion in PTC cells. Taken together, our findings suggest that HYOU1 promotes glycolysis and malignant progression in PTC cells via upregulating LDHB expression, providing a potential target for developing novel anticancer agents.

LncRNA-HCG18 regulates the viability, apoptosis, migration, invasion and epithelial-mesenchymal transition of papillary thyroid cancer cells via regulating the miR-106a-5p/PPP2R2A axis

The incidence of papillary thyroid cancer (PTC) has experienced a rapid increase in recent years. Long non-coding RNA-homo sapiens HLA complex group (HCG) 18 plays a regulatory role in cancers, but its role in PTC remained unknown. This study determined the expressions of HCG18, microRNA (miR)-106a-5p, and protein phosphatase 2 regulatory subunit B alpha (PPP2R2A) in PTC tissues and cells by qRT-PCR. ENCORI predicted the targeting relation between HCG18 and miR-106a-5p. TargetScan v7.2 predicted the targeting relation between miR-106a-5p and PPP2R2A. Dual-luciferase reporter assay was performed to validate the two targeting relations. The viability, migration, and invasion of PTC cells were detected by Cell Counting Kit-8, wound healing assay, and Transwell assay, respectively. The expressions of matrix metalloproteinase 2 (MMP-2), MMP-9, E-cadherin, N-cadherin, and Vimentin in TPC-1 and MDA-T68 cells were assessed by qRT-PCR and Western blot. It was found that HCG18 was down-regulated in PTC. Overexpressing HCG18 suppressed viability, migration, and invasion, promoted apoptosis, and inhibited miR-106a-5p expression in PTC cells. HCG18 interacted with miR-106a-5p, the expression of which was upregulated in PTC. Upregulating miR-106a-5p expression by lentivirus infection promoted viability, migration and invasion and inhibited apoptosis of PTC cells, reversed the effect of HCG18 on the biological behaviors of PTC cells, and promoted the expressions of MMP-2, MMP-9, E-cadherin, and Vimentin and downregulated E-cadherin expression in PTC cells. PPP2R2A, a direct target of miR-106a-5p, was downregulated in PTC, and HCG18 promoted PPP2R2A expression in PTC cells by sponging miR-106a-5p. Furthermore, PPP2R2A reversed the effects of miR-106a-5p on PTC cells. In conclusion, HCG18 suppressed viability, migration, invasion and epithelial–mesenchymal transition and promoted apoptosis of PTC cells via regulating the miR-106a-5p/PPP2R2A axis.

LINC01315 promotes the aggressive phenotypes of papillary thyroid cancer cells by sponging miR-497-5p.

Dysregulation of the long intergenic noncoding RNA 01315 (LINC01315) has recently been demonstrated in cancer. However, the role of LINC01315 in papillary thyroid cancer (PTC) has not been determined. We attempted to determine the function of LINC01315 in PTC. The levels of LINC01315 were higher in thyroid carcinoma tissues and cell lines compared with that in noncancerous tissues or normal cells, respectively. LINC01315 knockdown significantly inhibited the in vitro colony formation and invasion of PTC cells. Upregulation of LINC01315 produced opposite effects. Bioinformatic analysis and luciferase reporter assays indicated direct binding of miR-497-5p to LINC01315. Gain- and loss-of-function assays indicated that miR-497-5p acts as a suppressive miRNA in PTC. Furthermore, LINC01315 facilitated the growth and invasion of PTC cells by sponging miR-497-5p. Our results demonstrated the critical role of the LINC01315-miR-497-5p axis in the growth and invasion of PTC cells.

LncRNA FAM230B promotes the metastasis of papillary thyroid cancer by sponging the miR-378a-3p/WNT5A axis

Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in the progression of papillary thyroid cancer (PTC). In this study, we found consistently elevated expression levels of the lncRNA FAM230B in PTC tissues, both in newly generated RNA-seq data and in datasets from the GEO and TCGA databases. We demonstrated that the expression of FAM230B can be used for the diagnosis of PTC and is also strongly associated with lymph node metastasis. The potential biological functions of FAM230B and molecular mechanisms by which it regulates PTC progression were investigated. Functionally, FAM230B promoted the migration and invasion of PTC cells in vitro and in vivo. Mechanistically, FAM230B sponged miR-378a-3p and showed competitive binding to the 3′-UTR of WNT5A. FAM230B overexpression resulted in elevated WNT5A expression and thereby regulated the epithelial–mesenchymal transition in PTC cells. Finally, we verified that both miR-378a-3p overexpression and WNT5A silencing effectively offset the impacts of FAM230B on PTC cell migration and invasion. In conclusion, our study demonstrated the oncogenic function of the lncRNA FAM230B in PTC cells, providing a novel target for PTC diagnosis and therapy.

Long non-coding RNA OIP5-AS1 serves as a competing endogenous RNA to modulate X-linked inhibitor of apoptosis protein expression via adsorbing miR-429 in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is currently one of the most common endocrine tumors worldwide. Long non-coding RNA (LncRNA) is a vital regulator in the biological processes of diverse tumors. Hence, this work aimed to clarify the role and mechanism of lncRNA OIP5-AS1 in PTC progression. OIP5-AS1 and miR-429 expression levels in PTC tissues and cells were examined using qRT-PCR. Immunohistochemical staining (IHC) was applied to detect X-linked inhibitors of apoptosis protein (XIAP) expression in PTC tissues. A dual-luciferase reporter gene experiment was employed to validate the relationship for miR-429 and XIAP, miR-429 and OIP5-AS1. The regulatory effects of OIP5-AS1 on PTC cell proliferation, migration, and invasion was detected using the MTT, BrdU, Transwell and Western blot assays. In this work we reported that OIP5-AS1 expression was up-modulated in PTC tissues and cell lines. OIP5-AS1 overexpression enhanced the proliferation and metastasis of PTC cells, but the transfection of miR-429 mimics reversed the functions of OIP5-AS1 on the proliferation, migration, and invasion of PTC cells. Additionally, OIP5-AS1 was identified as a competitive endogenous RNA (ceRNA) that repressed miR-429, thereby increasing the expression level of XIAP. Taken together, the findings confirm that OIP5-AS1 accelerates PTC progression via modulating the miR-429/XIAP axis and imply that OIP5-AS1 is likely to be a therapeutic target for PTC.