00085472can120667-sup-t1-2_91k.pdf (91.16 kB)
Supplementary Tables 1-2 from miR-103/107 Promote Metastasis of Colorectal Cancer by Targeting the Metastasis Suppressors DAPK and KLF4
journal contributionposted on 2023-03-30, 21:03 authored by Hsin-Yi Chen, Yu-Min Lin, Hsiang-Ching Chung, Yaw-Dong Lang, Ching-Jung Lin, John Huang, Wei-Chi Wang, Feng-Mao Lin, Zhen Chen, Hsien-Da Huang, John Y.-J. Shyy, Jin-Tung Liang, Ruey-Hwa Chen
PDF file - 91K, Supplementary Tables include miR-103/107 Expression Status with relation to tumor stage, as well as Multivariate Analysis
ARTICLE ABSTRACTMetastasis is the major cause of poor prognosis in colorectal cancer (CRC), and increasing evidence supports the contribution of miRNAs to cancer progression. Here, we found that high expression of miR-103 and miR-107 (miR-103/107) was associated with metastasis potential of CRC cell lines and poor prognosis in patients with CRC. We showed that miR-103/107 targeted the known metastasis suppressors death-associated protein kinase (DAPK) and Krüppel-like factor 4 (KLF4) in CRC cells, resulting in increased cell motility and cell–matrix adhesion and decreased cell–cell adhesion and epithelial marker expression. miR-103/107 expression was increased in the presence of hypoxia, thereby potentiating DAPK and KLF4 downregulation and hypoxia-induced motility and invasiveness. In mouse models of CRC, miR-103/107 overexpression potentiated local invasion and liver metastasis effects, which were suppressed by reexpression of DAPK or KLF4. miR-103/107–mediated downregulation of DAPK and KLF4 also enabled the colonization of CRC cells at a metastatic site. Clinically, the signature of a miR-103/107 high, DAPK low, and KLF4 low expression profile correlated with the extent of lymph node and distant metastasis in patients with CRC and served as a prognostic marker for metastasis recurrence and poor survival. Our findings therefore indicate that miR-103/107–mediated repression of DAPK and KLF4 promotes metastasis in CRC, and this regulatory circuit may contribute in part to hypoxia-stimulated tumor metastasis. Strategies that disrupt this regulation might be developed to block CRC metastasis. Cancer Res; 72(14); 3631–41. ©2012 AACR.
BiomarkersMetastasis biomarkersCell SignalingCell adhesionGastrointestinal CancersLiver cancerOncogenes & Tumor SuppressorsSuppressors of metastasisProgression, Invasion & MetastasisCell adhesion and extracellular matrixMetastasisMigration and invasionTumor MicroenvironmentTumor-stromal cell interactions