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微小 RNA-181 在乳腺癌中发挥致癌作用,通过抑制 SPRY4。

MicroRNA‑181 serves an oncogenic role in breast cancer via the inhibition of SPRY4.

机构信息

Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

Department of Oncology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Mol Med Rep. 2018 Dec;18(6):5603-5613. doi: 10.3892/mmr.2018.9572. Epub 2018 Oct 22.

Abstract

Numerous microRNAs (miRs) have been implicated in breast cancer; however, the molecular mechanism is not fully understood. The present study examined the function and regulatory mechanism of miR‑181 in breast cancer. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to examine the RNA and protein expression. MTT assay, wound healing assay and transwell assay were conducted to study cell proliferation, migration and invasion. Luciferase reporter gene assay was used to confirm targeting relationship. The results suggested that the miR‑181 expression levels were significantly higher in breast cancer cell lines and clinical tissue samples. The increased expression of miR‑181 was markedly associated with higher clinical stage and lymph node metastasis. The patients with high miR‑181 expression demonstrated worse prognosis compared with those with a low expression of miR‑181. Small interfering RNA‑induced miR‑181 downregulation significantly inhibited breast cancer cell proliferation, migration and invasion in vitro, and tumor growth in vivo. Protein sprouty homolog 4 (SPRY4), downregulated in breast cancer tissues and cell lines, was observed to be a novel target gene of miR‑181. Downregulation of SPRY4 was significantly associated with breast cancer progression in addition to poor prognosis. Knockdown of SPRY4 rescued the inhibitory effects of miR‑181 downregulation on the malignant phenotypes of breast cancer cells. Thus, the present study demonstrated that miR‑181 serves a promoting role in breast cancer at least in part through the inhibition of SPRY4 expression. The present results expand the understanding of the miR‑181/SPRY4 axis' function during for the malignant progression of breast cancer.

摘要

许多 microRNAs(miRs)被认为与乳腺癌有关;然而,其分子机制尚不完全清楚。本研究探讨了 miR-181 在乳腺癌中的功能和调节机制。逆转录-定量聚合酶链反应和 Western blot 分析用于检测 RNA 和蛋白质表达。MTT assay、伤口愈合 assay 和 Transwell assay 用于研究细胞增殖、迁移和侵袭。荧光素酶报告基因 assay 用于证实靶向关系。结果表明,miR-181 在乳腺癌细胞系和临床组织样本中的表达水平显著升高。miR-181 表达的增加与较高的临床分期和淋巴结转移明显相关。miR-181 高表达的患者预后较 miR-181 低表达的患者差。小干扰 RNA 诱导的 miR-181 下调显著抑制乳腺癌细胞在体外的增殖、迁移和侵袭,并抑制体内肿瘤生长。蛋白 sprouty 同源物 4(SPRY4)在乳腺癌组织和细胞系中下调,被观察为 miR-181 的一个新的靶基因。SPRY4 的下调除了与不良预后相关外,还与乳腺癌的进展显著相关。SPRY4 的敲低挽救了 miR-181 下调对乳腺癌细胞恶性表型的抑制作用。因此,本研究表明 miR-181 在乳腺癌中至少部分通过抑制 SPRY4 的表达发挥促进作用。本研究结果扩展了对 miR-181/SPRY4 轴在乳腺癌恶性进展过程中功能的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa3d/6236310/05466ae857e2/MMR-18-06-5603-g00.jpg

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