Department of General Surgery, Minhang Hospital, Fudan University, Shanghai, China.
J Cell Biochem. 2019 Sep;120(9):14725-14734. doi: 10.1002/jcb.28733. Epub 2019 Apr 18.
Accumulating evidence has shown a critical role of long-non-coding RNAs (lncRNAs) during multiple tumor progression. However, the potential functions of LINC00504 in colon cancer as well as its mechanisms remain obscure. By lncRNA profiling, we identified LINC00504 as a novel oncogenic lncRNA in colon cancer. The lncRNA LINC00504 was markedly upregulated in colon cancer cell lines and specimens. LINC00504 increases viability and migration of colon cells in vitro. Furthermore, LINC00504 also enhances colon cancer xenograft tumors in vivo. We noted that LINC00504 regulates metabolism at a transcriptional level which influences multiple metabolic pathways, such as glucose metabolism, pentose phosphate pathway, and tricarboxylic acid cycle. Mechanistic study showed that LINC00504 could interact with c-Myc to promote chromatin recruitment of c-Myc and enhance its transactivation activity. Collectively, our results showed that LINC00504 serves as an important transcriptional regulator for c-Myc in colon cancer cells. LINC00504 can reprogram central metabolism in colon cancer cells implying that LINC00504 may serve as a potential target for therapeutic intervention.
越来越多的证据表明，长非编码 RNA（lncRNAs）在多种肿瘤进展过程中起着关键作用。然而，LINC00504 在结肠癌中的潜在功能及其机制仍不清楚。通过 lncRNA 分析，我们发现 LINC00504 是结肠癌中的一种新型致癌 lncRNA。lncRNA LINC00504 在结肠癌细胞系和标本中明显上调。LINC00504 增加了体外结肠细胞的活力和迁移。此外，LINC00504 还增强了体内结肠癌异种移植肿瘤的生长。我们注意到，LINC00504 在转录水平上调节代谢，影响多种代谢途径，如葡萄糖代谢、戊糖磷酸途径和三羧酸循环。机制研究表明，LINC00504 可以与 c-Myc 相互作用，促进 c-Myc 的染色质募集，并增强其转录激活活性。总之，我们的研究结果表明，LINC00504 作为一种重要的转录调节剂，在结肠癌细胞中发挥作用。LINC00504 可以重新编程结肠癌细胞中的中心代谢，这表明 LINC00504 可能是治疗干预的潜在靶点。
