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. 2017 Mar 14;8(11):17771-17784.
doi: 10.18632/oncotarget.14849.

SATB1 plays an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB

Affiliations

SATB1 plays an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB

Guiqin Song et al. Oncotarget. .

Abstract

Esophageal cancer is a highly aggressive malignancy with very poor overall prognosis. Given the strong clinical relevance of SATB1 in esophagus cancer and other cancers suggested by previous studies, the exact function of SATB1 in esophagus cancer development is still unknown. Here we showed that the knockdown of SATB1 in esophageal cancer cell lines diminished the cell proliferation, survival and invasion. Whole genome transcriptome analysis of SATB1 knockdown cells revealed the different gene expression profiles between TE-1 cells and MDA-MB-231 cells. Network analysis and functional experiments further identified FN1 and PDGFRB to be key downstream genes regulated by SATB1 in esophageal cancer cells. Importantly, FN1 and PDGFRB were found to be highly expressed in human esophageal cancer. In summary, we provided the first molecular evidence that SATB1 played an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.

Keywords: FN1; PDGFRB; SATB1; esophageal cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST

None.

Figures

Figure 1
Figure 1. SATB1 promotes TE-1 and EC-109 cell survival and migration
(A) MTT is employed to measure the cell viability in TE-1 and EC-109 cells. siN is the siRNA pool for control and siSATB1 is siRNA pool for SATB1; (B) Flow cytometry was performed to analyze the cell apoptosis. FL1-H is annexin V and FL2-H is PI. Western blot was performed to detect the cleaved PARP. Cell invasion/migration was evaluated by Transwell assays for (C) TE-1 cells and (D) EC-109 cells. The results are the mean ± SEM of three independent experiments.
Figure 2
Figure 2
Overlapping the down-regulated genes (A) and up-regulated genes (B) after knock-down of SATB1 in TE-1 cells (green part) or MDA-MB-231 cells under 2D (blue part) or 3D culture (red part). PPI network analysis those significantly changed genes after knock-down of SATB1 in TE-1 cells (C) or MDA-MB-231 cells under 2D (D) or 3D culture (E).
Figure 3
Figure 3
PPI network analysis of DEGs in (A) “biological regulation” , (B) “cellular process” , (C) “cell migration” pathways in TE-1 SATB1 knockdown cells. qRT-PCR and western blot were employed to validate (D) FN1 and (E) PDGFRB expression after knock-down of SATB1 in TE-1 cells. qRT-PCR and western blot were performed to validate FN1 (F) and PDGFRB (G) expression after knock-down of SATB1 in EC-109 cells, (H) Luciferease reporter assay.
Figure 4
Figure 4
MTT assay was employed to measure the cell proliferation in TE-1 cells (A) after overexpression FN1. and (B) after knockdown of SATB1 or/and overexpression of FN1 and (C) after overexpression PDGFRB and (D) after knockdown of SATB1 or/and overexpression of PDGFRB. Cell invasion/migration was evaluated by Transwell assays for (E) TE-1 cells overexpression of FN1 and (F) TE-1 cells overexpression of PDGFRB and (G) EC-109 cells overexpression of FN1 and (H). EC-109 cells overexpression of PDGFRB. The results are the mean ± SEM of three independent experiments.
Figure 5
Figure 5
(A, B, C and D) Oncomine analyses showed FN1 highly expressed in human esophageal squamous cell carcinoma and esophageal adenocarcinoma. (E, F, G, and H) Oncomine analyses showed PDGFRB highly expressed in human esophageal squamous cell carcinoma and esophageal adenocarcinoma.

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