The incidence of thyroid cancer remains high worldwide, and papillary thyroid cancer (PTC) is the most common type. Potassium Calcium-Activated Channel Subfamily N Member 4 ( KCNN4 ) has been reported as an oncogene in various cancers. We examined expression of KCNN4 in public databases and discovered that it is upregulated in PTC. We verified this finding using our own validated cohort and RNA sequencing data. We also found that KCNN4 is a diagnostic and prognostic biomarker that is associated with disease-free survival, immune infiltration, and several other clinicopathological features of PTC. Gene Set Enrichment Analysis indicated that apoptotic and epithelial-mesenchymal transition gene sets are both upregulated in PTC patients with higher KCNN4 levels. In PTC cell lines, silencing KCNN4 inhibited cell proliferation, migration and invasion. Moreover, quantitative real-time PCR and Western blotting indicated that silencing KCNN4 increased expression of apoptotic genes in PTC cells and reduced the expression of genes involved in their epithelial-mesenchymal transition. These results suggest that KCNN4 promotes PTC progression by inducing epithelial-mesenchymal transition and suppressing apoptosis, which suggests KCNN4 may be a useful diagnostic and prognostic biomarker of PTC.
Recently, the incidence of thyroid cancer is increasing worldwide. Papillary thyroid cancer (PTC) is the most common histological type of thyroid cancer. Whole‐transcriptome sequence analysis was performed to further understand the primary molecular mechanisms of the occurrence and progression of PTC. Results showed that Eva‐1 homolog A (EVA1A) may be a potential gene for the PTC‐associated gene in thyroid cancer. In this work, the role of EVA1A expression in thyroid cancer was investigated. Real‐time PCR was performed to detect the expression level of EVA1A in 43 pairs of PTC and four thyroid cancer cell lines. The Cancer Genome Atlas (TCGA) database was used to evaluate the relationship between the expression level of EVA1A and the pathological feature of PTC. The logistic regression analysis of the TCGA data set indicated that the expression of EVA1A was an independent risk factor for tumour, nde and metastasis (TNM) in PTC. This study shows the down‐regulation of EVA1A inhibited the colony formation, proliferation, migration and invasion of PTC cell lines. In the protein level, knockdown of EVA1A can regulate the expression of N‐cadherin, vimentin, Bcl‐xL, Bax, YAP and TAZ. This study indicated that EVA1A was an oncogene associated with PTC.
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.
In recent decades, the incidence of thyroid cancer (TC) has rapidly increased, leading us to explore the complex underlying mechanisms. We identified the gene Phospholipase C Delta 3 (PLCD3) as a potential oncogene in TC by conducting the whole transcriptome sequencing. Our study is to understand the oncogenic role of PLCD3 in TC. We verified the overexpression of PLCD3 in TC from The Cancer Genome Atlas, Gene Expression Omnibus databases, and a locally validated cohort. Clinical correlation analysis showed that PLCD3 expression was related to histological type, T stage, lymph node metastasis (LNM), and disease stage. The high expression of PLCD3 could be a distinguishing factor for TC and its LNM. The biological function was examined using small interfering RNA-transfected TC cell lines. Silenced PLCD3 could inhibit colony formation, migration, and invasion ability and promote apoptosis of TC cell lines. PLCD3 silencing reversed the epithelial-mesenchymal transition but induced the apoptotic progress. Further exploration revealed that PLCD3 might be associated with critical genes of the Hippo pathway. The expressions of RHOA, YAP1/TAZ, and their downstream targets were decreased significantly when PLCD3 was down-regulated. YAP1 overexpression rescued the tumor-suppressive effect caused by PLCD3 silencing. This study demonstrates that PLCD3 is an oncogene that supports tumorigenesis and progression in TC, and PLCD3 may be a potential target gene for TC treatment.
Thyroid cancer (TC) is the most common type of endocrine malignancy in humans, and its relative incidence has increased continuously in recent years. However, the primary molecular mechanisms of thyroid tumorigenesis and progression remain unclear. Papillary TC (PTC) is the most common subtype of TC. Recent studies have reported that one of the tumorigenesis and progression mechanisms is driven by genetic alterations that regulate the TC cell signaling pathway. In the present study, RNA sequencing (RNA-seq) was performed on 79 paired PTC and adjacent normal thyroid tissues to further study the molecular mechanisms of TC. Reverse transcription-quantitative PCR was used to detect the expression levels of LEM domain containing 1 (LEMD1) in 47 paired PTC and adjacent normal thyroid tissue samples. Initial analysis revealed that LEMD1 expression was significantly upregulated in TC tissues compared with that in normal tissues. The results of the thyroid RNA-seq datasets from The Cancer Genome Atlas were consistent with the RNA-seq analysis results of the present study. High LEMD1 expression increased the risk of lymph node metastasis in patients with TC. The biological function of LEMD1 on cell proliferation, migration, invasion and apoptosis was investigated in vitro via small interfering RNA and overexpression vector. Gene set enrichment analysis indicated that high LEMD1 expression was associated with epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway. Western blotting revealed that LEMD1 modulated the protein expression levels of E-cadherin, N-cadherin, vimentin, β-catenin and cleaved-caspase 3. In conclusion, the present results indicated that LEMD1 may drive TC cell tumorigenesis and progression by activating the Wnt/β-catenin signaling pathway and EMT.
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