LncRNA FAM83H-AS1 promotes triple-negative breast cancer progression by regulating the miR-136-5p/metadherin axis
LncRNA FAM83H-AS1 promotes triple-negative breast cancer progression by regulating the miR-136-5p/metadherin axis
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LncRNA FAM83H-AS1通过调节miR-136-5p/metadherin轴促进三阴性乳腺癌进展
DOI：
10.18632/aging.102832
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发表时间：
2020-02-29
期刊：
影响因子：
5.2
通讯作者：
Li, Qian
中科院分区：
文献类型：
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作者：
Han, Chunyong;Fu, Yiwei;Li, Qian
在这项研究中，我们评估了长链非编码RNA（lncRNA）FAM 83 H-AS 1在三阴性乳腺癌（TNBC）中的功能和调控。我们的数据显示，人TNBC细胞和组织中FAM 83 H-AS 1水平增加。TNBC细胞的增殖、迁移和侵袭通过FAM 83 H-AS 1抑制而降低，但通过FAM 83 H-AS 1过表达而增加。生物信息学分析表明，miR-136- 5 p是FAM 83 H-AS 1的潜在靶点。miR-136- 5 p表达在TNBC组织中降低，并且其过表达抑制TNBC细胞增殖、迁移和侵袭。miR-136- 5 p抑制逆转了FAM 83 H-AS 1沉默介导的对TNBC细胞增殖、迁移和侵袭的抑制，表明FAM 83 H-AS 1通过抑制miR-136- 5 p发挥其致癌作用。我们的数据鉴定了metadherin（MTDH）作为miR-136- 5 p的靶基因，并证明MTDH表达在人TNBC组织中增加，其诱导TNBC细胞的增殖、迁移和侵袭。重要的是，我们的体内数据显示，FAM 83 H-AS 1还促进TNBC小鼠异种移植物中的肿瘤生长。总之，我们的结果表明，FAM 83 H-AS 1作为致癌lncRNA发挥作用，在TNBC进展期间调节miR-136- 5 p和MTDH表达，并表明靶向FAM 83 H-AS 1/miR-136- 5 p/MTDH轴可以作为TNBC中的新治疗靶标。
In this study, we evaluated the function and regulation of the long non-coding RNA (lncRNA) FAM83H-AS1 in triple-negative breast cancer (TNBC). Our data show that the FAM83H-AS1 levels are increased in human TNBC cells and tissues. Proliferation, migration, and invasion of TNBC cells are decreased by FAM83H-AS1 suppression, but increased by FAM83H-AS1 overexpression. Bioinformatics analysis revealed that miR-136-5p is a potential target of FAM83H-AS1. MiR-136-5p expression is decreased in TNBC tissues, and its overexpression suppresses TNBC cell proliferation, migration, and invasion. MiR-136-5p suppression reverses the FAM83H-AS1 silencing-mediated inhibition of TNBC cell proliferation, migration, and invasion, suggesting that FAM83H-AS1 exerts its oncogenic effect by inhibiting miR-136-5p. Our data identify metadherin (MTDH) as the target gene of miR-136-5p, and demonstrate that the MTDH expression is increased in human TNBC tissues, which induces proliferation, migration, and invasion of TNBC cells. Importantly, our in vivo data show that FAM83H-AS1 also promotes tumor growth in TNBC mouse xenografts. Together, our results demonstrate that FAM83H-AS1 functions as an oncogenic lncRNA that regulates miR-136-5p and MTDH expression during TNBC progression, and suggest that targeting the FAM83H-AS1/miR-136-5p/MTDH axis may serve as a novel therapeutic target in TNBC.