Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3-c-Myc axis
Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3-c-Myc axis
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长非编码RNA CMPK2通过激活FUBP3-c-Myc轴促进结直肠癌进展
DOI：
10.1038/s41388-020-1266-8
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发表时间：
2020-03-20
期刊：
影响因子：
8
通讯作者：
Zhao, Liang
中科院分区：
文献类型：
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作者：
Gao, Qingzu;Zhou, Rui;Zhao, Liang
长非编码RNA(Long Non Coding RNAs，LncRNAs)已被证明在肿瘤发生发展中起关键作用。长非编码RNAs(Long Non Coding RNAs，LncRNAs)通过调节染色质动力学和基因表达，在肿瘤的发生、发展中发挥重要作用。然而，到目前为止，只有少数具有注释功能的lncRNAs在结直肠癌(CRC)的进展中被发现。在本研究中，lncCMPK2在结直肠癌组织中表达上调，并与临床分期和淋巴转移呈正相关。LncCMPK2的过表达促进了大肠癌细胞的增殖和细胞周期的转变。相反，沉默的lncCMPK2在体外和体内都限制了细胞的增殖。LncCMPK2定位于大肠癌细胞核，与远上游元件结合蛋白3(FUBP3)结合，并引导FUBP3与c-Myc基因的远上游元件(FUSE)结合，激活转录。LncCMPK2对FUBP3也有稳定作用。这些结果为了解lncCMPK2在结直肠癌进展中的作用机制提供了新的见解，并突出了其作为晚期结直肠癌生物标志物和治疗靶点的潜力。
Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer long noncoding RNAs (lncRNAs) have been known to play crucial roles in cancer development and progression by regulating chromatin dynamics and gene expression. However, only a few lncRNAs with annotated functions in the progression of colorectal cancer (CRC) have been identified to date. In the present study, the expression of lncCMPK2 was upregulated in CRC tissues and positively correlated with clinical stages and lymphatic metastasis. The overexpression of lncCMPK2 promoted the proliferation and cell cycle transition of CRC cells. Conversely, the silencing of lncCMPK2 restricted cell proliferation both in vitro and in vivo. lncCMPK2 was localized to the nucleus of CRC cells, bound to far upstream element binding protein 3 (FUBP3), and guided FUBP3 to the far upstream element (FUSE) of the c-Myc gene to activate transcription. lncCMPK2 also stabilized FUBP3. These results provide novel insights into the functional mechanism of lncCMPK2 in CRC progression and highlight its potential as a biomarker of advanced CRC and therapeutic target.