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长链非编码 RNA WEE2-AS1 通过调控 miR-32-5p/TOB1 轴促进三阴性乳腺癌细胞的增殖并抑制凋亡。

LncRNA WEE2-AS1 promotes proliferation and inhibits apoptosis in triple negative breast cancer cells via regulating miR-32-5p/TOB1 axis.

机构信息

Department of Thyroid Breast Surgery, HuBei Maternal and Child Health Hospital, No.745 Wuluo Road, Hongshan District, Wuhan, 430070, Hubei, China.

Department of Thyroid Breast Surgery, HuBei Maternal and Child Health Hospital, No.745 Wuluo Road, Hongshan District, Wuhan, 430070, Hubei, China.

出版信息

Biochem Biophys Res Commun. 2020 Jun 11;526(4):1005-1012. doi: 10.1016/j.bbrc.2020.01.170. Epub 2020 Apr 16.

DOI:10.1016/j.bbrc.2020.01.170
PMID:32307083
Abstract

Triple negative breast cancer (TNBC) is a malignant breast cancer subtype with poor prognosis. Recent studies have revealed the critical roles of dysregulated long non-coding RNAs (lncRNAs) in many cancer types, including TNBC. LncRNA WEE2 antisense RNA 1 (WEE2-AS1) has been reported to be able to promote the progression of hepatocellular carcinoma, but the function of WEE2-AS1 in TNBC is still unknown. Therefore, in this study, we specifically researched the role of WEE2-AS1 and probed its molecular mechanism in TNBC cells. Our results showed that WEE2-AS1 was up-regulated in TNBC cell lines, and WEE2-AS1 knockdown could inhibit TNBC cell proliferation, promote apoptosis, and suppress migration and invasion. Further, we found that miR-32-5p was down-regulated in TNBC cells and could be sponged by WEE2-AS1. Moreover, miR-32-5p could target its downstream gene transducer of ERBB2, 1 (TOB1), which was highly expressed and could play the oncogenic role in TNBC cells. Through rescue assays, we proved that WEE2-AS1/miR-32-5p/TOB1 axis could modulate cancer progression in TNBC cells. In conclusion, our results demonstrated the oncogenic function of lncRNA WEE2-AS1 in TNBC cells, providing a novel insight into TNBC therapy.

摘要

三阴性乳腺癌(TNBC)是一种预后不良的恶性乳腺癌亚型。最近的研究表明,失调的长非编码 RNA(lncRNA)在许多癌症类型中,包括 TNBC,起着关键作用。lncRNA WEE2 反义 RNA 1(WEE2-AS1)已被报道能够促进肝细胞癌的进展,但 WEE2-AS1 在 TNBC 中的功能仍不清楚。因此,在这项研究中,我们专门研究了 WEE2-AS1 的作用及其在 TNBC 细胞中的分子机制。我们的结果表明,WEE2-AS1 在 TNBC 细胞系中上调,WEE2-AS1 敲低可抑制 TNBC 细胞增殖,促进凋亡,并抑制迁移和侵袭。进一步,我们发现 miR-32-5p 在 TNBC 细胞中下调,并能被 WEE2-AS1 海绵吸附。此外,miR-32-5p 可以靶向其下游基因 ERBB2 转导物 1(TOB1),该基因在 TNBC 细胞中高表达并发挥致癌作用。通过挽救实验,我们证明了 WEE2-AS1/miR-32-5p/TOB1 轴可以调节 TNBC 细胞中的癌症进展。总之,我们的结果表明 lncRNA WEE2-AS1 在 TNBC 细胞中具有致癌功能,为 TNBC 治疗提供了新的见解。

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