Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China.
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China.
Cell Death Dis. 2019 May 16;10(6):378. doi: 10.1038/s41419-019-1598-x.
Ectopic expression of lncRNA-MALAT1 has been discovered in recurrent colorectal cancer (CRC) and metastatic sites in postsurgical patients, however, its biological mechanism remained unelucidated. Our study first revealed the novel roles of MALAT1 in promoting CRC metastasis through two mechanisms: first, MALAT1 binds miR-15 family members, to "de-inhibit" their effect on LRP6 expression, enhances β-catenin signaling, leading to elevated transcriptional levels of downstream target genes RUNX2. Second, MALAT1 binds SFPQ, and dissociates SFPQ/PTBP2 dimer to release free PTBP2, which elevates translational levels of RUNX2, through interacting with IRES domain in the 5'UTR of the corresponding RUNX2 mRNAs. Moreover, increased RUNX2 expression levels were detected in recurrent CRC tumors, which were closely associated with TMN stages, metastasis, as well as CRC patients' survival. Our study demonstrated that MALAT1 and RUNX2 may serve as two biomarkers for predicting the recurrence and metastasis of CRC patients.
长链非编码 RNA-MALAT1 的异位表达已在复发性结直肠癌（CRC）和术后患者的转移性部位中被发现，但它的生物学机制仍未阐明。我们的研究首次揭示了 MALAT1 通过两种机制促进 CRC 转移的新作用：首先，MALAT1 结合 miR-15 家族成员，“解除”它们对 LRP6 表达的抑制作用，增强β-连环蛋白信号，导致下游靶基因 RUNX2 的转录水平升高。其次，MALAT1 结合 SFPQ，并解离 SFPQ/PTBP2 二聚体以释放游离的 PTBP2，通过与相应 RUNX2 mRNAs 5'UTR 中的 IRES 结构域相互作用，提高 RUNX2 的翻译水平。此外，在复发性 CRC 肿瘤中检测到 RUNX2 表达水平升高，其与 TMN 分期、转移以及 CRC 患者的生存密切相关。我们的研究表明，MALAT1 和 RUNX2 可能作为预测 CRC 患者复发和转移的两个生物标志物。
