Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China.
Department of Cancer Prevention Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China.
Aging (Albany NY). 2023 Mar 13;15(5):1668-1684. doi: 10.18632/aging.204582.
Papillary thyroid cancer (PTC) is one of the most common malignant tumors in female, and estrogen can affect its progression. However, the targets and mechanisms of estrogen action in PTC remain unclear. Therefore, this study focuses on the relationship between estrogen-related genes (ERGs) expression and prognosis in PTC, particularly neuropeptide U (NMU), and its important role in tumor progression. Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, differentially expressed genes (DEGs) predominantly enriched in ERGs were identified between PTC and normal tissue. Then, we identified ERGs that contributed most to PTC prognosis, including Transducer of ERBB2 1 (TOB1), trefoil factor 1 (TFF1), phospholipase A and acyltransferase 3 (PLAAT3), NMU, kinesin family member 20A (KIF20A), DNA topoisomerase II alpha (TOP2A), tetraspanin 13 (TSPAN13), and carboxypeptidase E (CPE). In addition, we confirmed that NMU was highly expressed in PTC and explored the effect of NMU on PTC cells proliferation and . The results showed that the proliferative capacity of PTC cells was significantly reduced with NMU knockdown. Moreover, the phosphorylation levels of the Kirsten rat sarcoma virus (KRAS) signaling pathway were significantly lower with NMU knockdown. These results suggest that ERGs, especially NMU, may be novel prognostic indicators in PTC.
甲状腺乳头状癌 (PTC) 是女性中最常见的恶性肿瘤之一,而雌激素可影响其进展。然而,雌激素在 PTC 中的作用靶点和机制仍不清楚。因此,本研究重点关注雌激素相关基因 (ERGs) 表达与 PTC 预后之间的关系,特别是神经肽 U (NMU) 及其在肿瘤进展中的重要作用。基于癌症基因组图谱 (TCGA) 和基因表达综合数据库 (GEO),我们鉴定了 PTC 与正常组织之间差异表达的基因 (DEGs),这些基因主要富集在 ERGs 中。然后,我们确定了对 PTC 预后贡献最大的 ERGs,包括 ERBB2 受体转导物 1 (TOB1)、三叶因子 1 (TFF1)、磷脂酶 A 和酰基转移酶 3 (PLAAT3)、NMU、驱动蛋白家族成员 20A (KIF20A)、DNA 拓扑异构酶 II alpha (TOP2A)、四跨膜蛋白 13 (TSPAN13) 和羧肽酶 E (CPE)。此外,我们还证实了 NMU 在 PTC 中高表达,并探讨了 NMU 对 PTC 细胞增殖和 的影响。结果表明,NMU 敲低显著降低了 PTC 细胞的增殖能力。此外,NMU 敲低后 Kirsten 大鼠肉瘤病毒 (KRAS) 信号通路的磷酸化水平显著降低。这些结果表明,ERGs,特别是 NMU,可能是 PTC 的新型预后指标。