Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of papillary thyroid carcinoma via the BRAF-ERK1/2-P53 signaling pathway.

IF 5.4 2区医学 Q1 Medicine

Journal of Endocrinological Investigation Pub Date : 2024-11-02 DOI:10.1007/s40618-024-02481-5

Yuanhao Su, Lin Mei, Yongke Wu, Cheng Li, Tiantian Jiang, Yiyuan Zhao, Xin Feng, Tingkai Sun, Yunhao Li, Zhidong Wang, Yuanyuan Ji

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引用次数: 0

Abstract

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Xenotropic and polytropic retrovirus receptor 1 (XPR1), identified as a cellular receptor, plays roles in many pathophysiological processes. However, the underlying function and molecular mechanisms of XPR1 in PTC remain unclear. Therefore, this study aimed to elucidate the role of XPR1 in the process of PTC and the potential mechanisms.

Methods: RNA-sequencing was performed for gene differential expression analysis in PTC patients' tissues. Immunohistochemical assay, real-time PCR, and western blotting assay were used to determine the expression of XPR1, BRAF, and P53 in PTC tissues. The function of XPR1 on the progression of PTC was explored using in vitro and in vivo experiments. The molecular mechanism of XPR1 was investigated using gene silencing, ELISA, immunofluorescence, western blotting, and real-time PCR assays.

Results: We found that XPR1 was markedly upregulated in PTC tissues compared to adjacent noncancerous tissues, suggesting that high expression of XPR1 could be correlated with poor patient disease-free survival in PTC. In addition, the expression of BRAF and P53 in PTC tissues was substantially higher than in adjacent noncancerous tissues. Silencing of XPR1 reduced the proliferation, migration, and invasion capacities of TPC-1 cells in vitro and effectively inhibited the tumorigenecity of PTC in vivo. More importantly, silencing of XPR1 in TPC-1 cells significantly decreased the expression of XPR1, BRAF, and P53 both in vitro and in vivo. Interestingly, we demonstrated that XPR1 may positively activate the BRAF-ERK-P53 signaling pathway, further promoting PTC progression.

Conclusion: The findings reveal a crucial role of XPR1 in PTC progression and prognosis via the BRAF-ERK1/2-P53 signaling pathway, providing potential therapeutic targets for treating PTC.

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各向异性和多向性逆转录病毒受体1（XPR1）通过BRAF-ERK1/2-P53信号通路促进甲状腺乳头状癌的进展。

背景：甲状腺乳头状癌（PTC甲状腺乳头状癌（PTC）是最常见的甲状腺癌类型。异向性和多向性逆转录病毒受体 1（XPR1）被认为是一种细胞受体，在许多病理生理过程中发挥作用。然而，XPR1 在 PTC 中的潜在功能和分子机制仍不清楚。因此，本研究旨在阐明 XPR1 在 PTC 过程中的作用及其潜在机制：方法：对 PTC 患者组织进行 RNA 序列分析，以了解基因差异表达情况。方法：对 PTC 患者组织中的基因差异表达进行 RNA 序列分析，并通过免疫组化、实时 PCR 和 Western 印迹分析确定 XPR1、BRAF 和 P53 在 PTC 组织中的表达。通过体外和体内实验探讨了 XPR1 对 PTC 进展的作用。利用基因沉默、ELISA、免疫荧光、Western 印迹和实时 PCR 检测等方法研究了 XPR1 的分子机制：结果：我们发现，与邻近的非癌组织相比，XPR1在PTC组织中明显上调，这表明XPR1的高表达与PTC患者的无病生存率相关。此外，PTC 组织中 BRAF 和 P53 的表达也大大高于邻近的非癌组织。沉默 XPR1 降低了 TPC-1 细胞在体外的增殖、迁移和侵袭能力，并有效抑制了 PTC 在体内的致瘤性。更重要的是，在 TPC-1 细胞中沉默 XPR1 能显著降低 XPR1、BRAF 和 P53 在体外和体内的表达。有趣的是，我们证实 XPR1 可积极激活 BRAF-ERK-P53 信号通路，进一步促进 PTC 的进展：研究结果揭示了 XPR1 通过 BRAF-ERK1/2-P53 信号通路在 PTC 进展和预后中的关键作用，为治疗 PTC 提供了潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Endocrinological Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

8.10

自引率

7.40%

发文量

242

期刊介绍： The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.