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微小RNA-429通过靶向锌指E盒结合蛋白1抑制涎腺腺样囊性癌的进展和转移。

miR-429 suppresses progression and metastasis of salivary adenoid cystic carcinoma by targeting ZEB1.

作者信息

Li Juan, Zhao Hongwei

机构信息

The Affiliated Stomatological Hospital of Chongqing Medical University, 426 Songshi North Road, Longshan Street, Yubei District, Chongqing, 401147, China.

Chongqing Key Laboratory of Oral Diseases, Chongqing, 401147, China.

出版信息

J Mol Histol. 2025 Jul 9;56(4):224. doi: 10.1007/s10735-025-10504-5.

Abstract

miR-429 is a tumor suppressor that has been observed in various cancers. The exact mechanism by which miR-429 affects salivary adenoid cystic carcinoma(SACC) is not fully understood. Initially, the expression of miR-429 and zinc finger E-box-binding homeobox 1 (ZEB1) in tumor tissues and matched adjacent non-tumor tissues of SACC patients were inspected by quantitative real-time polymerase chain reaction. Next, CCK-8, wound healing, transwell, and dorsal root ganglion (DRG) co-culture models were used to explore the effects of miR-429 on SACC cell proliferation, migration, invasion, and perineural invasion (PNI). Finally, the downstream target genes of miR-429 were screened and validated through bioinformatics analysis and dual-luciferase reporter analysis, and the regulatory role of miR-429 on epithelial-mesenchymal transition (EMT) in SACC cells was explored. miR-429 was poorly expressed while ZEB1 was substantially expressed in SACC tumor tissues. Elevated levels of miR-429 led to a significant suppression of SACC cell of proliferation, migration, invasion, and PNI. ZEB1 was screened and validated as a downstream target gene of miR-429. High concentrations of miR-429 also markedly lowered the expression of ZEB1 in SACC cells, thereby inhibiting EMT. These results suggest that miR-429 is lowly expressed in SACC, may suppress progression and metastasis of SACC cells, and is associated with ZEB1 and the EMT pathway.

摘要

miR-429是一种在多种癌症中都有发现的肿瘤抑制因子。miR-429影响涎腺腺样囊性癌(SACC)的确切机制尚未完全明确。首先,通过定量实时聚合酶链反应检测SACC患者肿瘤组织及配对的相邻非肿瘤组织中miR-429和锌指E盒结合同源框1(ZEB1)的表达。接下来,使用CCK-8、伤口愈合、Transwell和背根神经节(DRG)共培养模型,探讨miR-429对SACC细胞增殖、迁移、侵袭和神经周围侵袭(PNI)的影响。最后,通过生物信息学分析和双荧光素酶报告基因分析筛选并验证miR-429的下游靶基因,并探讨miR-429对SACC细胞上皮-间质转化(EMT)的调控作用。在SACC肿瘤组织中,miR-429表达较低而ZEB1大量表达。miR-429水平升高导致SACC细胞的增殖、迁移、侵袭和PNI受到显著抑制。ZEB1被筛选并验证为miR-4家族成员29的下游靶基因。高浓度的miR-429也显著降低了SACC细胞中ZEB1的表达,从而抑制EMT。这些结果表明,miR-429在SACC中低表达,可能抑制SACC细胞的进展和转移,并且与ZEB1和EMT途径相关。

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