Xiwu Ouyang

Objectives: The mechanism of action of genes related to lactate metabolism in papillary thyroid carcinoma (PTC) is still unclear. In this study, key genes that play a role in PTC were selected from the known genes related to lactate metabolism, and their roles in promoting lactate metabolism in PTC cells were investigated. Methods: Through bioinformatics analysis and cell experiments, the roles of the relevant genes in lactate metabolism and their roles in the occurrence and development of PTC were verified. Results: Through bioinformatics analysis, 12 candidate genes were obtained. Through qRT-PCR experiments, it was confirmed that the expressions of TIMP1 and DPP4 were higher in thyroid papillary carcinoma than in normal PTC cells. By inhibiting the expression of TIMP1 and DPP4 using siRNA, the invasion and proliferation abilities of PTC could be reduced. Compared with normal thyroid cells, the contents of lactic acid and LDHA in PTC cells were higher. Knocking down the expression of TIMP1 and DPP4 would reduce the lactate production ability of PTC cells, and TIMP1 and DPP4 promoted the accumulation of lactate in PTC cells.Conclusions: In this study, by screening the differentially expressed lactate metabolism genes in PTC, different prognostic subtypes were constructed based on the molecular expression patterns. Multi-group student’s t-tests were conducted on the differential signaling pathways and tumor immune regulation of the prognostic subtypes, and a PTC prognosis prediction model was constructed. It was further confirmed that the lactate metabolism genes TIMP1 and DPP4 are highly expressed in PTC and can regulate the proliferation, invasion, metastasis and lactate metabolism of PTC cells.

Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the endocrine system, with its incidence increasing annually worldwide. Currently, despite the adoption of various treatment modalities, tumor invasion and metastasis constitute critical factors affecting the long-term survival of PTC patients. Adipocytes participate in regulating the malignant biological characteristics of tumor cells. However, the role of adipocytes in PTC carcinogenesis and progression remains poorly understood. Therefore, this study aims to investigate the role of adipocytes in PTC metastasis. 3T3L1-D cells were treated with differentiation medium to induce differentiation into adipocytes. PTC cells were cultured with adipocytes, and the PTC cell invasion ability was examined by transwell assay. The associated mechanisms were further investigated. Here, we found that the surrounding adipocytes could promote the invasion capacity of PTC cells via FATP2/TR4 signaling, and the inhibition of FATP2 or TR4 expression could reverse the invasion capacity of PTC cells. Furthermore, the preclinical investigation demonstrated that targeting this newly identified signaling with lipofermata (a FATP2-specific inhibitor) suppressed PTC progression. Together, these findings suggest that adipocytes in the PTC microenvironment may function via FATP2/TR4 signaling to regulate PTC progression, and targeting this newly identified adipocyte/FATP2/TR4 signaling axis may facilitate the development of novel therapeutic strategies for PTC.