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长链非编码 RNA ZEB2-AS1 通过表观遗传激活 ZEB2 促进三阴性乳腺癌的增殖、转移和上皮间质转化。

Long non-coding RNA ZEB2-AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple-negative breast cancer by epigenetically activating ZEB2.

机构信息

College of Biological Science and Technology, Weifang Medical University, Weifang, China.

Medicine Research Center, Weifang Medical University, Weifang, China.

出版信息

J Cell Mol Med. 2019 May;23(5):3271-3279. doi: 10.1111/jcmm.14213. Epub 2019 Mar 1.

DOI:10.1111/jcmm.14213
PMID:30825262
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6484319/
Abstract

The triple-negative breast cancer is the most malignant type of breast cancer. Its pathogenesis and prognosis remain poor despite the significant advances in breast cancer diagnosis and therapy. Meanwhile, long noncoding RNAs (LncRNAs) play a pivotal role in the progression of malignant tumors. In this study, we found that LncRNA-ZEB2-AS1 was dramatically up-regulated in our breast cancer specimens and cells (MDA231), especially in metastatic tumor specimens and highly invasive cells, and high lncRNA-ZEB2-AS1 expression is associated with clinicopathologic features and short survival of breast cancer patients. LncRNA-ZEB2-AS1 promotes the proliferation and metastasis of MDA231 cells in SCID mice. Thus, it is regarded as an oncogene in triple-negative breast cancer. It is mainly endo-nuclear and situated near ZEB2, positively regulating ZEB2 expression and activating the epithelial mesenchymal transition via the PI3K/Akt/GSK3β/Zeb2 signaling pathway. Meanwhile, EGF-induced F-actin polymerization in MDA231 cells can be suppressed by reducing lncRNA-ZEB2-AS1 expression. The migration and invasion of triple-negative breast cancer can be altered through cytoskeleton rearrangement. In summary, we demonstrated that lncRNA-ZEB2-AS1 is an important factor affecting the development of triple-negative breast cancer and thus a potential oncogene target.

摘要

三阴性乳腺癌是最恶性的乳腺癌类型。尽管在乳腺癌诊断和治疗方面取得了重大进展，但它的发病机制和预后仍然很差。同时，长链非编码 RNA（LncRNA）在恶性肿瘤的进展中起着关键作用。在这项研究中，我们发现 LncRNA-ZEB2-AS1 在我们的乳腺癌标本和细胞（MDA231）中显著上调，特别是在转移性肿瘤标本和高侵袭性细胞中，并且高表达 LncRNA-ZEB2-AS1 与乳腺癌患者的临床病理特征和短生存期相关。LncRNA-ZEB2-AS1 促进 MDA231 细胞在 SCID 小鼠中的增殖和转移。因此，它被认为是三阴性乳腺癌中的致癌基因。它主要位于核内，靠近 ZEB2，通过 PI3K/Akt/GSK3β/Zeb2 信号通路正向调节 ZEB2 的表达并激活上皮间质转化。同时，通过降低 LncRNA-ZEB2-AS1 的表达可以抑制 EGF 诱导的 MDA231 细胞中的 F-肌动蛋白聚合。通过细胞骨架重排可以改变三阴性乳腺癌的迁移和侵袭。总之，我们证明了 LncRNA-ZEB2-AS1 是影响三阴性乳腺癌发展的重要因素，因此是潜在的致癌基因靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/d0f76445e786/JCMM-23-3271-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/47b09eefb13c/JCMM-23-3271-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/5173e3c32bed/JCMM-23-3271-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/d753e850d473/JCMM-23-3271-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/357905be093e/JCMM-23-3271-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/6ed500a758b6/JCMM-23-3271-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/d0f76445e786/JCMM-23-3271-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/47b09eefb13c/JCMM-23-3271-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/5173e3c32bed/JCMM-23-3271-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/d753e850d473/JCMM-23-3271-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/357905be093e/JCMM-23-3271-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/6ed500a758b6/JCMM-23-3271-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c37/6484319/d0f76445e786/JCMM-23-3271-g006.jpg

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