LOC389641 promotes papillary thyroid cancer progression by regulating the EMT pathway.

Aim: Thyroid cancer (TC) is one of the most common types of endocrine malignancy and poses a significant challenge to human health. The long noncoding RNA 389641 (LOC389641) has been found to be associated with many types of cancer. However, the function of LOC389641 in papillary TC (PTC) remains unknown. Our aim is to explore LOC389641 expression and its role in TC. Materials & methods: The function of LOC389641 was determined by colony formation, migration and invasion assays in PTC. Western blot assays were performed to determine the biomarker of epithelial-mesenchymal transition. Results: In this study, we show that LOC389641 is involved in PTC, which suggests that it may be a target for TC therapies.

Lysophosphatidic Acid Receptor 5 (LPAR5) Plays a Significance Role in Papillary Thyroid Cancer via Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin (mTOR) Pathway.

BACKGROUND Thyroid cancer is the most common endocrine system malignancy. Scientists have done considerable research into the molecular mechanisms involved, but many mechanisms remain undiscovered. MATERIAL AND METHODS We performed a comprehensive analysis of the whole-transcriptome resequencing derived from thyroid tissues and paired papillary thyroid cancer (PTC) and showed that lysophosphatidic acid receptor 5 (LPAR5) is strongly overexpressed in thyroid carcinoma. Then, we used TPC-1 and KTC-1 to explore the effect of LPAR5 knockdown on colony formation, migration, proliferation, invasion, and apoptosis of PTC cell line cells. AKT activator was used for the recovery test. Finally, we designed proteomic experiments to explore the role of LPAR5 in the AKT pathway and the EMT process. RESULTS Cell function experiments showed that LPAR5 knockdown can significantly induce apoptosis of KTC-1 and TPC-1 cells. Furthermore, LPAR5 can promote PTC metastasis and tumorigenesis by activating the PI3K/AKT pathway and decreasing its cancer-promoting effect when using AKT agonist. We also found that LPAR5 can regulate the expression of EMT-related proteins, which affect invasion and migration. CONCLUSIONS In summary, downregulation of LPAR5 expression can inhibit the physiological process of PTC, and this phenomenon is related to the PI3K/AKT pathway and EMT.

Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial-mesenchymal transition.

Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti-oncogene associated with PTC. By RT-qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss-function experiments in TC cell lines (KTC-1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future. SIGNIFICANCE OF THE STUDY: Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. By whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues, author discovered that scavenger receptor class A member 5 (SCARA5) might be crucial anti-oncogene associated with PTC. Furthermore, knocking-down of SCARA5 in TC cell line can increase the function of cells proliferation, colony formation, migration, and invasion. Author also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins.

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.

NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT.

Papillary thyroid cancer (PTC) is the most frequent type of malignant thyroid cancer, but its molecular mechanisms remain unknown. To better understand the tumorigenesis and progression of PTC, we conducted a comprehensive analysis of the whole-transcriptome resequencing of paired PTC and normal thyroid tissues. Nectin cell adhesion molecule 4 (NECTIN4) was significantly overexpressed in thyroid carcinoma compared with that in matched normal tissue. We also assessed the relation between the expression level of NECTIN4 and the clinicopathological features of PTC in The Cancer Genome Atlas database, and results showed that upregulated NECTIN4 is associated with lymph node metastasis (P<0.001) and tumor size (P=0.017). The biological function of NECTIN4 was also investigated by using the PTC cell lines TPC-1 and KTC-1. In vitro experiments demonstrated that NECTIN4 downregulation significantly inhibits the colony formation, proliferation, migration, and invasion of PTC cell lines. NECTIN4 could modulate the expression of epithelial-mesenchymal transition-related proteins via the PI3K/AKT pathway, and SC79, an AKT phosphorylation activator, could reverse the si-RNA knockdown effect. In addition, after the use of AKT inhibitors (LY 294,002), we found that SiRNA have similar effect with AKT inhibitors. Taking the results together, the current study shows that NECTIN4 has important biological implications in the tumorigenesis and metastasis of PTC and may be a potential therapeutic target for the disease.