Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
The Fourth Clinical School of Nanjing Medical University, Nanjing 210009, China.
Comput Math Methods Med. 2022 Jan 12;2022:5203839. doi: 10.1155/2022/5203839. eCollection 2022.
Studies revealed an important role of microRNAs (miRNAs) in multiple cancers, including breast cancer. In the present study, we evaluated the role and function of miR-641 in breast cancer.
The expression level of miR-641 in breast cancer cell lines (Hs-578T, MCF7, HCC1937, and MAD-MB-231) was determined by real-time PCR. Functional analyses, including CCK-8 assay, transwell assay, wound-healing assay, and apoptosis detection, were carried out to explore the roles of miRNA-641 in malignant behaviors of breast cancer. Luciferase report assay was used to investigate the regulatory association of miRNA-641 with its potential targets.
The expression levels of miR-641 were downregulated, while the expression levels of nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) were increased in breast cancer cell lines. The results showed that miR-641 repressed proliferation and migration/invasion and promoted apoptosis of breast cancer cells. NUCKS1, a positive regulator of phosphatidylinositol-3-kinases (PI3K)/protein-serine-threonine kinase (AKT) pathway, was confirmed as a direct target of miR-641. The of treatment of the PI3K agonist, 740Y-P, could abrogate the antioncogenic potentials of miR-641 in breast cancer cells.
miR-641 functioned as a tumor suppressor through the PI3K/AKT signaling pathway via targeting NUCKS1 in breast cancer.
研究表明 microRNAs（miRNAs）在多种癌症中发挥着重要作用，包括乳腺癌。本研究旨在评估 miR-641 在乳腺癌中的作用和功能。
通过实时 PCR 测定乳腺癌细胞系（Hs-578T、MCF7、HCC1937 和 MAD-MB-231）中 miR-641 的表达水平。进行 CCK-8 测定、Transwell 测定、划痕愈合测定和凋亡检测等功能分析，以探讨 miR-641 在乳腺癌恶性行为中的作用。利用荧光素酶报告试验研究 miR-641 与其潜在靶标的调控关系。
miR-641 的表达水平下调，而核酪蛋白激酶和周期蛋白依赖性激酶底物 1（NUCKS1）的表达水平在乳腺癌细胞系中升高。结果表明，miR-641 抑制了乳腺癌细胞的增殖、迁移/侵袭，并促进了其凋亡。NUCKS1 是磷脂酰肌醇-3-激酶（PI3K）/丝氨酸-苏氨酸激酶（AKT）通路的正调节剂，被确认为 miR-641 的直接靶标。PI3K 激动剂 740Y-P 的处理可以消除 miR-641 在乳腺癌细胞中的抗肿瘤潜能。
miR-641 通过靶向 NUCKS1 抑制 PI3K/AKT 信号通路，在乳腺癌中发挥肿瘤抑制作用。
