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富含脯氨酸蛋白 11(PRR11)通过激活 EGFR 信号通路促进皮肤鳞状细胞癌的进展。

Proline-rich 11 (PRR11) promotes the progression of cutaneous squamous cell carcinoma by activating the EGFR signaling pathway.

机构信息

Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Mol Carcinog. 2023 May;62(5):613-627. doi: 10.1002/mc.23510. Epub 2023 Feb 2.

DOI:10.1002/mc.23510
PMID:36727626
Abstract

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignancies, and its incidence rate is increasing worldwide. Proline-rich 11 (PRR11) has been reported to be involved in the occurrence and development of various tumors. However, the role of PRR11 in cSCC remains unknown. In the present study, we observed upregulated expression of PRR11 in cSCC tissues and cell lines. Knockdown of PRR11 in the cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing cell cycle arrest during the G1/S phase transition, promoted cell apoptosis, and reduced cell migration and invasion in vitro. Conversely, overexpression of PRR11 promoted cell proliferation, decreased cell apoptosis, and enhanced cell migration and invasion. PRR11 knockdown also inhibited cSCC tumor growth in a mouse xenograft model. Mechanistic investigations by RNA sequencing revealed that 891 genes were differentially expressed genes between cells with PRR11 knockdown and control cells. Enrichment analysis of different genes showed that the epidermal growth factor receptor (EGFR) signaling pathway was the top enriched pathway. We further validated that PRR11 induced EGFR pathway activity, which contributed to cSCC progression. These data suggest that PRR11 may serve as a novel therapeutic target in cSCC.

摘要

皮肤鳞状细胞癌 (cSCC) 是最常见的皮肤恶性肿瘤之一,其发病率在全球范围内呈上升趋势。富含脯氨酸蛋白 11 (PRR11) 已被报道参与各种肿瘤的发生和发展。然而,PRR11 在 cSCC 中的作用尚不清楚。在本研究中,我们观察到 PRR11 在 cSCC 组织和细胞系中表达上调。在 cSCC 细胞系 A431 和 SCL-1 中敲低 PRR11 通过诱导 G1/S 期转换时的细胞周期停滞抑制细胞增殖,促进细胞凋亡,并减少体外细胞迁移和侵袭。相反,过表达 PRR11 促进细胞增殖,减少细胞凋亡,并增强细胞迁移和侵袭。PRR11 敲低也抑制了小鼠异种移植模型中的 cSCC 肿瘤生长。RNA 测序的机制研究表明,PRR11 敲低和对照细胞之间有 891 个差异表达基因。不同基因的富集分析表明,表皮生长因子受体 (EGFR) 信号通路是最富集的通路。我们进一步验证了 PRR11 诱导 EGFR 通路活性,这有助于 cSCC 的进展。这些数据表明,PRR11 可能成为 cSCC 的一个新的治疗靶点。

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