scholarly journals m5C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in papillary thyroid carcinoma

2020 ◽  
Author(s):  
Fei Li ◽  
Qingmei Deng ◽  
Xiaoxi Pang ◽  
Shan Huang ◽  
Jingmiao Zhang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Microenvironment ◽  
Thyroid Carcinoma ◽  
Cell Counting ◽  
Cell Infiltration ◽  
Support Vector ◽  
Diagnostic Model ◽  
Papillary Thyroid ◽  
Signature Genes ◽  
Score Model

Abstract BackgroundRecently, immune response modulation at epigenetic level is illustrated in studies, but it is still unclear about the possible function of RNA 5-methylcytosine (m5C) modification in the cell infiltration within tumor microenvironment (TME).MethodsIn this study, the m5C modification patterns from altogether 493 papillary thyroid carcinoma (PTC) samples were assessed completely according to 9 m5C regulators. Afterwards, the modification patterns were correlated with the cell infiltration features in TME. The m5C modification patterns in tumor samples were quantified through the principal component analysis (PCA) algorithms to establish the m5C-score. Moreover, this study mined the signature genes related to the m5C-score, constructed the PTC diagnostic model by the support vector machine (SVM) method, and verified its accuracy based on samples in TCGA and GEO databases. The effects of 5 potential drugs based on the PTC m5C-score model in PTC cells were investigated through in vitro and in vivo assays (i.e., cell counting kit 8 and xenograft model). ResultsA total of 3 different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above 3 identified patterns. It was revealed that, evaluating m5C modification patterns in single tumor samples helped to estimate the stromal activity in TME, expression of immune checkpoint genes, and prognosis for patients. Typically, a low m5C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. Few effective immune infiltration was seen in high m5C-score subtype, indicating the dismal patient survival. Finally, this study constructed a diagnostic model using the 10 signature genes highly related to the m5C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out 5 potential drugs for PTC based on this m5C-score model. ConclusionsAccording to findings in the present study, m5C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m5C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME and to better guide clinical diagnosis as well as immunotherapies.

scholarly journals m5C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fei Li ◽  
Qingmei Deng ◽  
Xiaoxi Pang ◽  
Shan Huang ◽  
Jingmiao Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Patient Survival ◽  
Cell Infiltration ◽  
Diagnostic Model ◽  
Response Modulation ◽  
Signature Genes ◽  
Differentiation Degree ◽  
Prognostic Outcome ◽  
Immune Response Modulation ◽  
Score Model

Recently, immune response modulation at the epigenetic level is illustrated in studies, but the possible function of RNA 5-methylcytosine (m5C) modification in cell infiltration within the tumor microenvironment (TME) is still unclear. Three different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above three identified patterns. A low m5C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. A small amount of effective immune infiltration was seen in the high m5C-score subtype, indicating the dismal patient survival. Our study constructed a diagnostic model using the 10 signature genes highly related to the m5C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out five potential drugs for PTC based on this m5C-score model. m5C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m5C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME.

scholarly journals A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma

Open Medicine ◽  
2021 ◽  
Vol 17 (1) ◽  
pp. 22-33
Author(s):  
Yarong Yang ◽  
Wenjuan Hua ◽  
Mei Zeng ◽  
Liling Yu ◽  
Baijun Zhang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Messenger Rna ◽  
Subcellular Fractionation ◽  
Suppressive Effect ◽  
Differentiated Thyroid Carcinoma ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Papillary Thyroid

Abstract Papillary thyroid carcinoma (PTC) is the most frequent histological type of differentiated thyroid carcinoma. Long noncoding RNAs (lncRNAs) have been widely reported to play a key role in human malignancies, and PTC is included. This study aimed to find out the functions and mechanism of lncRNA LINC00475 in PTC. LINC00475 was upregulated in PTC cells and was mainly located in the cytoplasm according to reverse-transcription polymerase chain reaction analyses and subcellular fractionation assays. As shown by cell counting kit-8 assays, ethynyl deoxyuridine incorporation assays, wound healing assays, and transwell assays, LINC00475 knockdown suppressed cell viability, proliferation, migration, and invasion. Mechanistically, LINC00475 upregulated the expression of messenger RNA zinc finger CCHC-type containing 12 (ZCCHC12) by binding to miR-376c-3p. ZCCHC12 was a direct target gene of miR-376c-3p in PTC cells. The relationship between miR-376c-3p and LINC00475 (or ZCCHC12) in PTC cells was probed by luciferase reporter assays, RNA pulldown assays, and RNA immunoprecipitation assays. In addition, both mRNA and protein levels of ZCCHC12 were downregulated due to miR-376c-3p overexpression or LINC00475 silencing. ZCCHC12 overexpression partially reversed the suppressive effect of LINC00475 knockdown on malignant behaviors of PTC cells. In conclusion, LINC00475 promotes PTC cell proliferation, migration, and invasion by upregulating ZCCHC12 via the interaction with miR-376c-3p.

scholarly journals BRAFV600E in Papillary Thyroid Carcinoma Is Associated with Increased Programmed Death Ligand 1 Expression and Suppressive Immune Cell Infiltration

Thyroid ◽  
2014 ◽  
Vol 24 (9) ◽  
pp. 1385-1393 ◽  
Author(s):  
Trevor E. Angell ◽  
Melissa G. Lechner ◽  
Julie K. Jang ◽  
Adrian J. Correa ◽  
Jonathan S. LoPresti ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Papillary Thyroid ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals LncRNA GAS8-AS1 suppresses papillary thyroid carcinoma cell growth through the miR-135b-5p/CCND2 axis

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
NingHeng Chen ◽  
DeTao Yin ◽  
Bing Lun ◽  
XueLi Guo
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Cell Growth ◽  
Thyroid Carcinoma ◽  
Cell Cycle Progression ◽  
Gene Prediction ◽  
Tumor Formation ◽  
Cell Counting ◽  
Papillary Thyroid ◽  
Downstream Target

AbstractThe aim of the present study was to investigate the potential role of GAS8 antisense RNA 1 (GAS8-AS1) in papillary thyroid carcinoma (PTC). PcDNA3.1-GAS8-AS1 and si-GAS8-AS1, miR-135b-5p mimic and si-CCND2 were transfected into PTC cells. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8). QRT-PCR was used to determine expressions of GAS8-AS1, miR-135b-5p, and CCND2, and Western blot were detected protein level of CCND2. The miRNA target gene prediction site TargetScan was used to predict potential targets of GAS8-AS1 and miR-135b-5p. Cell cycle progression was analyzed by flow cytometry. We found that GAS8-AS1 was down-regulated in PTC cell lines and inhibited proliferation and cycle of PTC cell. GAS8-AS1 directly targets miR-135b-5p, and GAS8-AS1 could regulate a downstream target of miR-135b-5p, Cyclin G2 (CCNG2), in an miR-135b-5p-mediated manner. In addition, we also proved that overexpressed GAS8-AS1 inhibited tumor formation in vivo. GAS8-AS1 suppresses PTC cell growth through the miR-135b-5p/CCND2 axis.

scholarly journals Analysis of the prognostic significance and potential mechanisms of lncRNAs associated with m6A methylation in papillary thyroid carcinoma

2021 ◽  
Author(s):  
Yinde Huang ◽  
Xin Li ◽  
Wenbin Chen ◽  
Yuzhen He ◽  
Song Wu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Microenvironment ◽  
Thyroid Carcinoma ◽  
Immune Checkpoint ◽  
Prognostic Model ◽  
Prognostic Markers ◽  
Clinicopathological Characteristics ◽  
Papillary Thyroid ◽  
The Relationship ◽  
Pan Cancer

Abstract Background : m6A methylation-related long non-coding RNAs (lncRNAs) play a significant role in the progression of various tumors and can be used as prognostic markers. However, whether m6A-related lncRNAs also play the same function as prognostic markers in papillary thyroid carcinoma (PTC) remains unclear. Methods : Consensus cluster analysis was performed to divide PTC samples obtained from The Cancer Genome Atlas database into two clusters according to the expression of m6A-related lncRNAs. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to create and verify a prognostic model. Furthermore, the relationship among risk scores, clusters, programmed death-ligand 1 (PD-L1), tumor microenvironment (TME), clinicopathological characteristics, immune infiltration, immune checkpoint, and tumor mutation burden (TMB) was analyzed. In addition, a nomogram was created, and subsequently, the drug sensitivity of lncRNAs in the prognostic model was analyzed. Finally, the relationship between these lncRNAs and prognosis in pan-cancer was investigated. Results: The prognosis, RAS, BRAF, M, and TME were found to be different in two clusters. The prognostic model included three lncRNAs: PSMG3-AS1 , BHLHE40-AS1 , and AC016747.3 . The risk score was associated with clusters, PD-L1, tumor microenvironment, clinicopathological characteristics, immune cell infiltration, immune checkpoint, and TMB, and thus, risk score was confirmed as useful prognostic indicators. Differentially expressed lncRNAs are involved in many malignancies and can be identified as cancer prognostic makers. Conclusion : According to our research, we can regard m6A-related lncRNAs involved in the procession of PTC as a biomarker of PFS for PTC patients, and pan-cancer.

scholarly journals Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma

2021 ◽  
Vol 18 (6) ◽  
pp. 9016-9032
Author(s):  
Jie Qiu ◽  
◽  
Maolin Sun ◽  
Chuanshan Zang ◽  
Liwei Jiang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Circular Rna ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Regulatory Mechanisms ◽  
Recursive Feature Elimination ◽  
Support Vector ◽  
Papillary Thyroid ◽  
Competitive Endogenous Rna

<abstract> <p>&gt;This study aimed to identify potential circular RNA (circRNA), microRNA (miRNA) and mRNA biomarkers as well as their underlying regulatory mechanisms in papillary thyroid carcinoma (PTC). Three microarray datasets from the Gene Expression Omnibus database as well as expression data and clinical phenotype from The Cancer Genome Atlas (TCGA) were downloaded, followed by differential expression, functional enrichment, protein–protein interaction (PPI), and module analyses. The support vector machine (SVM)-recursive feature elimination (RFE) algorithm was used to screen the key circRNAs. Finally, the mRNA-miRNA-circRNA regulatory network and competitive endogenous RNA (ceRNA) network were constructed. The prognostic value and clinical correlations of key mRNAs were investigated using TCGA dataset, and their expression was validated using the UALCAN database. A total of 1039 mRNAs, 18 miRNAs and 137 circRNAs were differentially expressed in patients with PTC. A total of 37 key circRNAs were obtained using the SVM-RFE algorithm, whereas 46 key mRNAs were obtained from significant modules in the PPI network. A total of 11 circRNA-miRNA pairs and 40 miRNA-mRNA pairs were predicted. Based on these interaction pairs, 46 circRNA-miRNA-mRNA regulatory pairs were integrated, of which 8 regulatory pairs in line with the ceRNA hypothesis were obtained, including two circRNAs (circ_0004053 and circ_0028198), three miRNAs (miR-199a-5p, miR-199b-5p, and miR-7-5p), and five mRNAs, namely <italic>APOA2</italic>, <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic>, and <italic>TIMP1</italic>. Survival analysis showed that <italic>LPAR5</italic> expression was associated with patient survival. <italic>APOA2</italic> expression showed significant differences between metastatic and non-metastatic tumors, whereas <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic> and <italic>TIMP1</italic> showed significant differences between metastatic and non-metastatic lymph nodes. Overall, we identified several potential targets and regulatory mechanisms involved in PTC. <italic>APOA2</italic>, <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic>, and <italic>TIMP1</italic> may be correlated with PTC metastasis.</p> </abstract>

scholarly journals Analysis of the prognostic significance and potential mechanisms of lncRNAs associated with m6A methylation in papillary thyroid carcinoma

2021 ◽  
Author(s):  
Yinde Huang ◽  
Xin Li ◽  
Wenbin Chen ◽  
Yuzhen He ◽  
Song Wu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Microenvironment ◽  
Thyroid Carcinoma ◽  
Immune Checkpoint ◽  
Prognostic Model ◽  
Prognostic Markers ◽  
Clinicopathological Characteristics ◽  
Papillary Thyroid ◽  
The Relationship ◽  
Pan Cancer

Abstract Background : m6A methylation-related long non-coding RNAs (lncRNAs) play a significant role in the progression of various tumors and can be used as prognostic markers. However, whether m6A-related lncRNAs also play the same function as prognostic markers in papillary thyroid carcinoma (PTC) remains unclear. Methods : Consensus cluster analysis was performed to divide PTC samples obtained from The Cancer Genome Atlas database into two clusters according to the expression of m6A-related lncRNAs. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to create and verify a prognostic model. Furthermore, the relationship among risk scores, clusters, programmed death-ligand 1 (PD-L1), tumor microenvironment (TME), clinicopathological characteristics, immune infiltration, immune checkpoint, and tumor mutation burden (TMB) was analyzed. In addition, a nomogram was created, and subsequently, the drug sensitivity of lncRNAs in the prognostic model was analyzed. Finally, the relationship between these lncRNAs and prognosis in pan-cancer was investigated. Results: The prognosis, RAS, BRAF, M, and TME were found to be different in two clusters. The prognostic model included three lncRNAs: PSMG3-AS1 , BHLHE40-AS1 , and AC016747.3 . The risk score was associated with clusters, PD-L1, tumor microenvironment, clinicopathological characteristics, immune cell infiltration, immune checkpoint, and TMB, and thus, risk score was confirmed as useful prognostic indicators. Differentially expressed lncRNAs are involved in many malignancies and can be identified as cancer prognostic makers. Conclusion : According to our research, we can regard m6A-related lncRNAs involved in the procession of PTC as a biomarker of PFS for PTC patients, and pan-cancer.

scholarly journals Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/β-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Wencheng Dai ◽  
Xiaoxia Jin ◽  
Liang Han ◽  
Haijing Huang ◽  
Zhenhua Ji ◽  
...  
Keyword(s):  
Stem Cell ◽  
Papillary Thyroid Carcinoma ◽  
Tumor Microenvironment ◽  
Thyroid Carcinoma ◽  
Cancer Stem Cell ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Potential Target ◽  
Bioinformatics Databases ◽  
Non Coding Rnas

Abstract Exosomal long non-coding RNAs (lncRNAs) are crucial factors that mediate the extracellular communication in tumor microenvironment. DOCK9 antisense RNA2 (DOCK9-AS2) is an exosomal lncRNA which has not been investigated in papillary thyroid carcinoma (PTC). Based on the result of differentially expressed lncRNAs in PTC via bioinformatics databases, we discovered that DOCK9-AS2 was upregulated in PTC, and presented elevation in plasma exosomes of PTC patients. Functionally, DOCK9-AS2 knockdown reduced proliferation, migration, invasion, epithelial-to-mesenchymal (EMT) and stemness in PTC cells. PTC-CSCs transmitted exosomal DOCK9-AS2 to improve stemness of PTC cells. Mechanistically, DOCK9-AS2 interacted with SP1 to induce catenin beta 1 (CTNNB1) transcription and sponged microRNA-1972 (miR-1972) to upregulate CTNNB1, thereby activating Wnt/β-catenin pathway in PTC cells. In conclusion, PTC-CSCs-derived exosomal lncRNA DOCK9-AS2 activated Wnt/β-catenin pathway to aggravate PTC progression, indicating that DOCK9-AS2 was a potential target for therapies in PTC.

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