Department of Physiology and Hypoxic Biomedicine, Institute of Special Environmental Medicine, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, 226019, Jiangsu, China.
Department of Pathology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, China.
BMC Cancer. 2022 May 12;22(1):533. doi: 10.1186/s12885-022-09603-3.
As a metastasis-related protein, NEDD9 has been reported in breast cancer (BC) metastasis research. However, there are few studies on the upstream regulators of NEDD9, especially involving the potential role of miRNAs. The purpose of this study was to explain whether miR-107 potentially regulates NEDD9, which may lead to invasion and metastasis of BC.
MCF-7 and MDA-MB-231 cells were transduced with lentiviruses to construct stably transduced cells with miR-107 overexpression, miR-107 silencing or empty vectors. A luciferase reporter assay was performed to verify the binding of miR-107 and NEDD9. The scratch test and Transwell assay were used to measure cell migration and invasion ability, respectively. For the study of metastasis in vivo, we injected MDA-MB-231 cells into the fat pad of nude mice to develop an orthotopic breast cancer model.
We found that NEDD9 expression correlates with the prognosis of BC patients. In BC cell lines, NEDD9 was positively correlated with cell migration ability. Further research revealed that miR-107 inhibited NEDD9 expression by targeting the 3'-untranslated region of NEDD9. Overexpression of miR-107 suppressed the expression of NEDD9, thereby inhibiting the invasion, migration and proliferation of BC cells, but interference with miR-107 promoted the expression of NEDD9 as well as invasion, migration and proliferation. In an in vivo model, overexpression of miR-107 decreased the expression of NEDD9 and inhibited tumour growth, invasion and metastasis; however, these effects were reversed by inhibiting miR-107.
These findings indicated the potential role of miR-107 in regulating NEDD9 in the invasion, migration and proliferation of BC.
作为一种转移相关蛋白，NEDD9 已在乳腺癌（BC）转移研究中被报道。然而，关于 NEDD9 的上游调节剂的研究较少，特别是涉及 miRNA 的潜在作用。本研究旨在解释 miR-107 是否可能调节 NEDD9，从而导致 BC 的侵袭和转移。
使用慢病毒转导 MCF-7 和 MDA-MB-231 细胞，构建 miR-107 过表达、miR-107 沉默或空载体稳定转染细胞。通过荧光素酶报告基因检测验证 miR-107 与 NEDD9 的结合。划痕试验和 Transwell 试验分别用于测量细胞迁移和侵袭能力。为了研究体内转移，我们将 MDA-MB-231 细胞注射到裸鼠脂肪垫中，建立原位乳腺癌模型。
我们发现 NEDD9 的表达与 BC 患者的预后相关。在 BC 细胞系中，NEDD9 与细胞迁移能力呈正相关。进一步研究表明，miR-107 通过靶向 NEDD9 的 3'非翻译区抑制 NEDD9 的表达。miR-107 的过表达抑制了 NEDD9 的表达，从而抑制了 BC 细胞的侵袭、迁移和增殖，但干扰 miR-107 促进了 NEDD9 的表达以及侵袭、迁移和增殖。在体内模型中，miR-107 的过表达降低了 NEDD9 的表达并抑制了肿瘤的生长、侵袭和转移；然而，这些作用通过抑制 miR-107 而被逆转。
这些发现表明 miR-107 在调节 NEDD9 促进 BC 的侵袭、迁移和增殖方面具有潜在作用。
