Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Bioengineered. 2022 May;13(5):11822-11831. doi: 10.1080/21655979.2022.2074110.
Cell migration inducing hyaluronidase 1 (CEMIP) mediates catabolism of hyaluronan, and participates in the cell metastasis, invasion, and motility. Dysregulated CEMIP expression was associated with progression and prognosis of tumors. The role of CEMIP in papillary thyroid carcinoma (PTC) remains unknown. Our study showed that CEMIP was upregulated in both tissues and cells of PTC. Silencing of CEMIP reduced cell proliferation and suppressed migration and invasion of PTC. Protein expression of phosphorylated STAT3 (Signal Transducer And Activator Of Transcription 3) (p-STAT3), AKT (p-AKT) and p65 (p-p65) were decreased by CEMIP silencing in PTC cells. Pyruvate dehydrogenase kinase 4 (PDK4) over-expression attenuated CEMIP silencing-induced decrease in p-STAT3, p-AKT and p-p65. Silencing of CEMIP-induced decrease in cell proliferation and metastasis in PTC were restored by over-expression of STAT3. CEMIP functioned as an oncogenic gene in PTC through PDK4-mediated activation of STAT3/AKT/NF-κB pathway.
细胞迁移诱导透明质酸酶 1(CEMIP)介导透明质酸的分解代谢,并参与细胞转移、侵袭和迁移。CEMIP 表达失调与肿瘤的进展和预后有关。CEMIP 在甲状腺乳头状癌(PTC)中的作用尚不清楚。我们的研究表明,CEMIP 在 PTC 的组织和细胞中均上调。沉默 CEMIP 可降低 PTC 细胞的增殖,并抑制其迁移和侵袭。沉默 CEMIP 可降低 PTC 细胞中磷酸化 STAT3(Signal Transducer And Activator Of Transcription 3)(p-STAT3)、AKT(p-AKT)和 p65(p-p65)的蛋白表达。丙酮酸脱氢酶激酶 4(PDK4)过表达可减弱 CEMIP 沉默诱导的 p-STAT3、p-AKT 和 p-p65 减少。过表达 STAT3 可恢复 CEMIP 沉默诱导的 PTC 细胞增殖和转移减少。CEMIP 通过 PDK4 介导的 STAT3/AKT/NF-κB 通路的激活在 PTC 中发挥致癌基因的作用。