大约70%-80%的乳腺癌(BCs)表达雌激素受体(ER-positive)。微RNA (miRNAs) 是一类小的内源性非编码RNA，对乳腺癌等癌症的发展和进展起到重要的调节作用。miRNA 缺乏促进乳腺癌的发展。MiR-143-5p 是乳腺癌中最常见的异常表达的miRNA之一，但其作为肿瘤抑制基因的作用尚不清楚。利用TCGA和StarBase数据库分析了乳腺组织中miR-143-3p和-5p的表达，进行了乳腺癌亚型和生存分析。收集了临床样品，建立了细胞培养物，并进行了基因表达分析，按照先前的研究进行了蛋白表达、荧光素酶报告基因、创伤愈合、DAPI染色、细胞周期、集落形成、球体、CD44 FACS和增殖试验，按照不同的方案进行了实验。在本研究中，我们发现BC组织中的miR-143-3p和miR-143-5p水平都比正常乳腺组织低很多，并且低miR-143表达预示着ER+ BC患者预后不良。深入分析发现miR-143-5p与DNA结合蛋白高迁移率族AT钩2(HMGA2)的3' 未翻译区(UTR)中存在3个结合位点。荧光素酶报告基因实验和Western blot分析表明，HMGA2是BC细胞中miR-143-5p的直接靶标。此外，我们还证明miR-143-5p的恢复表达能够抑制ER+ BC细胞的转移相关特征，包括减少肿瘤细胞迁移、增加E-cadherin的表达，降低vimentin和N-cadherin的表达。此外，miR-143-5p减少细胞增殖、细胞周期进入和干细胞特性，同时适度促进细胞凋亡。最后，患者样本通路分析表明这些机制在BC中也是活跃的。总的来说，我们的发现为miR-143-5p在BC发展中作为抗癌生物功能的认识提供了新的线索，该miRNA可以通过直接靶向HMGA2来治疗ER+ BC，这可能是一种有前景的新治疗方法。版权所有 © 2023 Elsevier Inc. 保留所有权利。

About 70%-80% of breast cancers (BCs) express estrogen receptors (ER-positive). MicroRNAs (miRNAs) are a group of small endogenous noncoding RNAs that play a critical regulatory role in cancer development and progression, including in BC. MiRNA deficiency promotes the development of BCs. MiR-143-5p is one of the most commonly dysregulated miRNAs in BC but its role as a tumor suppressor remains unclear.MiR-143-3p and -5p expression in breast tissue was analyzed using TCGA and StarBase databases. Expression in BC subclasses and survival analyses were conducted. Clinical samples were collected, cell cultures created, and gene expression assays performed following previous studies. Protein expression, luciferase reporter, wound healing, DAPI staining, cell cycle, colony formation, spheroid, CD44 FACS, and proliferation assays were conducted following various protocols.Here, we find that both miR-143-3p and miR-143-5p levels are considerably lower in BC tissue compared to normal breast tissue and low miR-143 expression predicts poor prognosis in ER+ BC patients. In-depth analyses identified 3 miR-143-5p binding sites in the 3' untranslated region (UTR) of the DNA binding protein High Mobility Group AT-Hook 2 (HMGA2). Luciferase reporter assays using wild-type and mutant HMGA2 3'UTR sequences and Western blot analyses demonstrated that HMGA2 is a direct and bona fide miR-143-5p target in BC cells. In addition, we show that restoration of miR-143-5p expression suppresses metastasis-related features of ER+ BC cells, including reduced tumor cell migration, increased E-cadherin expression, and decreased vimentin and N-cadherin expression. Furthermore, miR-143-5p reduces cell proliferation, cell cycle entry, and stemness, while promoting apoptosis moderately. Finally, patient sample pathway analyses demonstrated that these mechanisms are also active in BC.Altogether, our findings shed new light on miR-143-5p's anticancer biological functions in BC progression by directly targeting HMGA2. This suggests that restoration of miR-143-5p could be a promising new therapeutic approach for the treatment of ER+ BC.Copyright © 2023 Elsevier Inc. All rights reserved.