Jingfeng Gu1, Guiqi Wang1, Haixia Liu2, Chaohui Xiong3. 1. Department of Gastrointestinal Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 2. The Second Surgery Department, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei, China. 3. Department of Ophthalmology, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.
Abstract
OBJECTIVES: SATB2 has been shown to be markedly reduced in colorectal cancer (CRC) tissues relative to paired normal controls; however, the mechanism behind remains not well understood. To investigate why SATB2 was down-regulated in CRC, we attempted to analyse it from the angle of miRNA-mRNA modulation. MATERIALS AND METHODS: SATB2 expression was detected in CRC tissues using immunohistochemistry and verified using real-time PCR on mRNA level, followed by analysis of clinicopathological significance of its expression. Metastatic variation of CRC cells was evaluated both in vivo and in vitro. To find out the potential miRNA that directly regulate the SATB2, luciferase reporter assay was performed following the bioinformatic prediction. RESULTS: SATB2 was confirmed to be closely linked with the metastasis and shorter overall survival of CRC in our own cases. Silencing of SATB2 was shown to be able to promote the metastatic ability of CRC cells in vivo, enhancing the epithelial-mesenchymal transition (EMT). Mechanistically, miR-34c-5p was identified to be a novel miRNA that can directly modulate the SATB2. It turned out that the promoter of miR-34c-5p was methylated, which leads to the repression of miR-34c-5p in CRC. Treatment with 5-Aza-dC can reasonably and significantly restore the level of miR-34c-5p in CRC cells relative to control, thereby down-regulating the SATB2. CONCLUSIONS: Together, our study revealed that SATB2 targeted by methylated miR-34c-5p can suppress the metastasis, weakening the EMT in CRC.
OBJECTIVES:SATB2 has been shown to be markedly reduced in colorectal cancer (CRC) tissues relative to paired normal controls; however, the mechanism behind remains not well understood. To investigate why SATB2 was down-regulated in CRC, we attempted to analyse it from the angle of miRNA-mRNA modulation. MATERIALS AND METHODS:SATB2 expression was detected in CRC tissues using immunohistochemistry and verified using real-time PCR on mRNA level, followed by analysis of clinicopathological significance of its expression. Metastatic variation of CRC cells was evaluated both in vivo and in vitro. To find out the potential miRNA that directly regulate the SATB2, luciferase reporter assay was performed following the bioinformatic prediction. RESULTS:SATB2 was confirmed to be closely linked with the metastasis and shorter overall survival of CRC in our own cases. Silencing of SATB2 was shown to be able to promote the metastatic ability of CRC cells in vivo, enhancing the epithelial-mesenchymal transition (EMT). Mechanistically, miR-34c-5p was identified to be a novel miRNA that can directly modulate the SATB2. It turned out that the promoter of miR-34c-5p was methylated, which leads to the repression of miR-34c-5p in CRC. Treatment with 5-Aza-dC can reasonably and significantly restore the level of miR-34c-5p in CRC cells relative to control, thereby down-regulating the SATB2. CONCLUSIONS: Together, our study revealed that SATB2 targeted by methylated miR-34c-5p can suppress the metastasis, weakening the EMT in CRC.
Authors: Jacob Elebro; Margareta Heby; Alexander Gaber; Björn Nodin; Liv Jonsson; Richard Fristedt; Mathias Uhlén; Karin Jirström; Jakob Eberhard Journal: J Transl Med Date: 2014-10-17 Impact factor: 5.531