Abstract：
Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.
摘要：
长非编码RNA(lncRNA)已显示驱动癌症进展。然而,lncRNAs的功能和早期乳腺癌(BC)的潜在机制很少被研究.浸润性导管原位癌（DCIS）的数据集，使用TCGA和GEO数据库中的浸润性导管BC（IDC）和正常乳腺组织进行生物信息学分析。LncRNACARMN在早期BC中被确定为肿瘤抑制因子，并且与更好的预后有关。CARMN过表达抑制MMP2介导的BC迁移和EMT。进一步分析显示CARMN位于细胞核中并在乳腺上皮细胞中作为增强子RNA(eRNA)发挥作用。机械上,CARMN结合蛋白DHX9通过RNA下拉和质谱(MS)测定鉴定,并且其还与MMP2启动子结合以激活其转录。作为诱饵，CARMN竞争性结合DHX9并阻断MMP2转录激活，从而抑制BC细胞的转移和EMT。这些发现揭示了CARMN作为肿瘤抑制因子在转移中的重要作用以及早期BC进展的潜在生物标志物。
