Long noncoding RNA CERS6-AS1 functions as a malignancy promoter in breast cancer by binding to IGF2BP3 to enhance the stability of CERS6 mRNA
Long noncoding RNA CERS6-AS1 functions as a malignancy promoter in breast cancer by binding to IGF2BP3 to enhance the stability of CERS6 mRNA
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DOI：
10.1002/cam4.2675
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发表时间：
2019-11-08
期刊：
影响因子：
4
通讯作者：
Zhou, Tian
中科院分区：
文献类型：
--
作者：
Bao, Gang;Huang, Jianjun;Zhou, Tian
乳腺癌是世界上女性死亡率最高的疾病，其特点是乳腺癌细胞不可避免地增殖和转移。越来越多的证据证实，lncRNAs在BC的发生发展中起着重要作用。LncRNA CERS6-AS1是一个新的发现，其在BC中的作用和分子机制尚未被研究。本研究发现CERS6-AS1在BC组织和细胞中高表达。CERS6-AS1促进BC细胞增殖，抑制细胞凋亡。分子机制研究发现CERS6与CERS6-AS1(或IGF2BP3)在BC中的表达呈正相关。此外，IGF2BP3是CERS6-AS1的RNA结合蛋白，CERS6-AS1通过与IGF2BP3结合来促进CERS6mRNA的稳定性。最后，营救性实验证实CERS6的过表达挽救了CERS6-AS1缺陷对体内外BC进展的抑制作用。综上所述，CERS6-AS1通过与IGF2BP3结合从而增强CERS6mRNA的稳定性，从而促进了BC的进展，为BC改善预后提供了新的潜在治疗靶点。
Breast cancer (BC) leads to the highest mortality in women worldwide, characterized by inevitable proliferation and metastasis of BC cells. Mounting evidence confirm that lncRNAs play a significant role in the tumorigenesis and development of BC. lncRNA CERS6-AS1 is a novel discovery, and its role and molecular mechanism in BC has not been studied. In this study, it was discovered that CERS6-AS1 was overexpressed in BC tissues and cells. CERS6-AS1 accelerated cell proliferation and suppressed cell apoptosis in BC. Moreover, molecular mechanism exploration uncovered that there was a positive association between CERS6 and CERS6-AS1 (or IGF2BP3) expression in BC. Furthermore, IGF2BP3 serves as a RNA-binding protein for CERS6-AS1 and CERS6-AS1 promoted CERS6 mRNA stability by binding to IGF2BP3. In the end, rescue experiments verified that overexpression of CERS6 rescues the inhibition of CERS6-AS1 deficiency on BC progression in vitro and vivo. Taken together, these evidences suggested that CERS6-AS1 promoted the progression of BC by binding to IGF2BP3 and thus enhancing the stability of CERS6 mRNA, providing a new underlying therapeutic target for BC to improve prognosis.