<p>ANGPTL4 Promotes the Proliferation of Papillary Thyroid Cancer via AKT Pathway</p>

Abstract

Although papillary thyroid carcinoma (PTC) is associated with a generally favorable prognosis, about 15% of patients present recurrence and distant metastasis in the next decade leading to death. Angiopoietin-like 4 (ANGPTL4) is secreted to circulation and belongs to the angiopoietin-like proteins. The expression of ANGPTL4 was increased in several solid tumor tissues compared to corresponding paracancerous tissues. ANGPTL4 was identified as pro-tumorigenic protein, including stimulating tumor cell growth, promoting tumor metastasis. However, the clinical significance and biological function of ANGPTL4 in PTC is still unclear. Hence, the purpose of this study was to evaluate the role of ANGPTL4 in PTC, investigating the possibility of whether ANGPTL4 could become a novel target for PTC therapy. Methods: We investigated the expression level of ANGPTL4 and pAKT in PTC and paracancerous tissue by immunohistochemistry. We determined the effect of ANGPTL4 in PTC cell proliferation through cell counting kit-8 (CCK-8) and cell cycle by flow cytometry analysis. Furthermore, the correlation between ANGPTL4 expression levels and PTC cell proliferation from the TCGA data set was analyzed by GSEA. We explored the role of ANGPTL4 on the phosphorylation of AKT and proliferation in PTC cells via overexpression or knockdown assays and AKT inhibitor assay. Results: In the present study, we found that ANGPTL4 was highly expressed in both protein and mRNA level in PTC compared with adjacent noncancerous tissues or benign nodule. ANGPTL4 expression increased according to thyroid tumor progression. ANGPTL4 level was positively correlated with the size of PTC. ANGPTL4 increased cell proliferation and decreased cell cycle arrest of PTC. Knockdown of ANGPTL4 inhibited the phosphorylation of AKT. ANGPTL4 regulated PTC cell proliferation through AKT signaling pathway. Conclusion: Our findings suggested that ANGPTL4 was increased in PTC compared with adjacent noncancerous tissues, and ANGPTL4 increased cell proliferation and inhibited cell cycle arrest in PTC cells via promoting AKT phosphorylation. The study may provide fundamental information to suggest its suitability as a target for the treatment of PTC.

An immune gene signature to predict prognosis and immunotherapeutic response in lung adenocarcinoma

“…ANGPTL4 has been identified as an oncogene in papillary thyroid carcinoma (PTC). Upregulation of ANGPTL4 promotes PTC cell proliferation and reduces PTC cell cycle arrest 36 . Overexpression of PLK1 promotes the proliferation of renal cell carcinoma (RCC) cells and inhibits apoptosis 37 .…”

“…It is possible to evaluate tumor immunogenicity and response to ICIs therapy by analyzing cell cycle-related genes 47 . In this study, two genes (ANGPTL4 and PLK1) of the IGSPP that we constructed were involved in the regulation of the tumor cell cycle 36 , 39 . GSEA of the IGSPP subgroups showed that genes in the IGSPP high-risk group were significantly enriched in cell cycle-related pathways (Fig.…”

SGLT2 inhibition restrains thyroid cancer growth via G1/S phase transition arrest and apoptosis mediated by DNA damage response signaling pathways

“…All these tissues were embedded in paraffin wax. In addition, 10 fine needle aspiration thyroid samples (6 cases of benign and 4 cases of malignancy) were collected for RNA-Seq [ 17 ]. The basic and pathological characteristics of PTC patients were extracted from medical records.…”

A Novel Secreted Protein-Related Gene Signature Predicts Overall Survival and Is Associated With Tumor Immunity in Patients With Lung Adenocarcinoma

“…Nevertheless, in vivo experiments indicated its efficacy in regulating mucosal immune responses and fighting bacterial and viral infections. ANGPTL4 and IGFBP1 are secreted into the plasma and are involved in cell energy metabolism (60)(61)(62).…”