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MicroRNA-384 通过靶向 ACVR1 抑制乳腺癌的进展。

MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1.

机构信息

Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China.

The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China.

出版信息

Oncol Rep. 2018 Jun;39(6):2563-2574. doi: 10.3892/or.2018.6385. Epub 2018 Apr 20.

Abstract

Breast cancer is the leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancer cases and has a poorer prognosis than other subtypes. Moreover, the treatment for breast cancer, especially for TNBC, remains unsatisfactory. Therefore, novel therapies are urgently needed. Microribonucleic acids (miRNAs) are a class of biomarkers and therapeutic targets in many types of cancers. In the present study, the expression of miR-384 was explored in GSE58606 and in fresh breast cancer tissues by qPCR. The results showed that miR-384 was decreased in breast cancer, especially in TNBC. The results of MTT, colony formation, soft agar, Transwell migration, wound healing and the tumorigenesis assay demonstranted that overexpression of miR-384 inhibited the proliferation and migration of breast cancer in vitro and in vivo; knockdown of miR-384 enhanced the proliferation and migration of breast cancer. In addition, luciferase assay showed that Activin A receptor type 1 (ACVR1) was a direct target of miR-384 and is involved in the inhibitory effects of miR-384 on breast cancer progression. Furthermore, this study indicated that ACVR1 activated the Wnt/β-catenin signaling pathway in breast cancer. In conclusion, our findings revealed functional and mechanistic links between miR-384 and ACVR1 in the progression of breast cancer. miR-384 not only plays an important role in the progression of breast cancer, but has promise as a potential therapeutic target for breast cancer especially for TNBC.

摘要

乳腺癌是全球女性癌症相关死亡的主要原因。三阴性乳腺癌(TNBC)占所有乳腺癌病例的 15%,其预后比其他亚型差。此外,乳腺癌的治疗方法,尤其是 TNBC 的治疗方法,仍然不尽如人意。因此,迫切需要新的治疗方法。微小 RNA(miRNAs)是许多类型癌症的生物标志物和治疗靶点。本研究通过 qPCR 探讨了 miR-384 在 GSE58606 和新鲜乳腺癌组织中的表达。结果表明,miR-384 在乳腺癌中,尤其是在 TNBC 中表达降低。MTT、集落形成、软琼脂、Transwell 迁移、划痕愈合和肿瘤发生实验结果表明,miR-384 的过表达抑制了乳腺癌在体外和体内的增殖和迁移;miR-384 的下调增强了乳腺癌的增殖和迁移。此外,荧光素酶报告基因实验表明,激活素 A 受体 1(ACVR1)是 miR-384 的直接靶基因,并参与 miR-384 对乳腺癌进展的抑制作用。此外,本研究表明,ACVR1 在乳腺癌中激活了 Wnt/β-catenin 信号通路。总之,本研究揭示了 miR-384 和 ACVR1 在乳腺癌进展中的功能和机制联系。miR-384 不仅在乳腺癌的进展中发挥重要作用,而且作为乳腺癌的潜在治疗靶点具有很大的潜力,特别是对于 TNBC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbc/5983929/cc0dab64dac6/OR-39-06-2563-g00.jpg

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