KLF5-induced lncRNA IGFL2-AS1 promotes basal-like breast cancer cell growth and survival by upregulating the expression of IGFL1
KLF5-induced lncRNA IGFL2-AS1 promotes basal-like breast cancer cell growth and survival by upregulating the expression of IGFL1
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KLF5诱导的lncRNA IGFL2-AS1通过上调IGFL1的表达促进基底样乳腺癌细胞的生长和存活
DOI：
10.1016/j.canlet.2021.04.016
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发表时间：
2021-05-31
期刊：
影响因子：
9.7
通讯作者：
Chen, Ceshi
中科院分区：
文献类型：
--
作者：
Wang, Haixia;Shi, Yujie;Chen, Ceshi
基底细胞样乳腺癌(BLBC)是乳腺癌中恶性程度最高的亚型，预后不良。Kruppellike factor5(KLF5)是BLBC中的一种致癌转录因子。KLF5通过调节lncRNAs转录促进BLBC的机制尚未完全阐明。在本研究中，我们发现LncRNA IGFL2-AS1是KLF5的下游靶基因，IGFL2-AS1介导了KLF5的促增殖和生存功能。此外，我们还证明了IGFL2-AS1的功能是通过两种独立的机制上调其邻近基因IGFL1的转录。一方面，核IGFL2-AS1促进在IGFL1基因增强子上形成KLF5/TEAD4转录复合体。另一方面，胞质IGFL2-AS1抑制针对IGFL1基因的miR4795-3p的表达。TNFa通过KLF5诱导IGFL2-AS1和IGFL1的表达。综上所述，本研究结果提示IGFL2-AS1和IGFL1可能成为BLBC治疗的新靶点。
Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer and has a poor prognosis. Kruppellike factor 5 (KLF5) is an oncogenic transcription factor in BLBCs. The mechanism by which KLF5 promotes BLBC by regulating the transcription of lncRNAs has not been fully elucidated. In this study, we discovered that lncRNA IGFL2-AS1 is a downstream target gene of KLF5 and that IGFL2-AS1 mediates the pro-proliferation and prosurvival functions of KLF5. Additionally, we demonstrated that IGFL2-AS1 functions by upregulating the transcription of its neighboring gene IGFL1 via two independent mechanisms. On the one hand, nuclear IGFL2-AS1 promotes the formation of a KLF5/TEAD4 transcriptional complex at the IGFL1 gene enhancer. On the other hand, cytoplasmic IGFL2-AS1 inhibits the expression of miR4795-3p, which targets the IGFL1 gene. TNFa induces the expression of IGFL2-AS1 and IGFL1 through KLF5. Taken together, the results of this study indicate that IGFL2-AS1 and IGFL1 may serve as new therapeutic targets for BLBCs.