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/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.
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.
Objective. Unexplained infertility (UIF) or recurrent pregnancy loss (RPL) affects 10%–15% of couples in their reproductive years and is multifactorial and not completely elucidated. In this study, we attempt to determine the endometrial expression pattern of non-coding RNA activated by DNA damage (NORAD) in women with UIF and RPL, as well as its clinical significance. Methods. The microarray dataset GSE165004 was used to identify differentially expressed RNAs in the endometrial samples between women with RPL and fertile women and between women with UIF and fertile women. A total of 142 women were included in this retrospective analysis, including 32 women with UIF, 48 women with RPL, and 62 fertile women. The relative expression level of NORAD in the endometrial tissues was quantified by qRT-PCR. Results. NORAD stood out as an only overlapped lncRNA among differentially expressed RNAs in the endometrial samples between RPL and fertile women and between UIF and fertile women. It was showed that the endometrial tissues of UIF and RPL both were demonstrated with lower relative expression levels of NORAD (UIF: 2.09 ± 0.68; RPL: 1.98 ± 0.65) than the endometrial tissues of normal fertility (4.32 ± 1.04) (
P
<
0.001
). Pearson correlation analysis demonstrated that the serum level of E2 was negatively correlated with the relative expression level of NORAD in the endometrial tissues of UIF (r = −0.630) and RPL (r = −0.696). Results of ROC curves showed that the endometrial expression of NORAD could be used to differentiate RPL and UIF with an AUC of 0.977 (95% CI: 0.956–0.999) and 0.970 (95% CI: 0.941–0.998), sensitivity of 0.873 and 0.955, and specificity of 0.845 and 0.948, respectively. Conclusion. The findings obtained from the study showed that the low endometrial expression of NORAD was linked to fertility-related problems, such as UIF and RPL.
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