SATB2 induces stem-like properties and promotes epithelial-mesenchymal transition in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevailing malignancies, and the molecular mechanisms underlying HCC tumorigenesis remain to be further clarified. The aim of our present study was to determine the biological functions and clinical significance of SATB2 in HCC. Quantitative RT-PCR was performed to detect SATB2 mRNA expression in HCC tissues and cells. Cell proliferation, migration and invasion were investigated by MTT assay and transwell assay. Western blotting was performed to evaluate the protein expression levels. Tumor xenografts were established to explore the effects of SATB2 on HCC tumor growth in vivo. Our results indicated that SATB2 was highly expressed in HCC tissues and cell lines, and its high expression was closely correlated with aggressive clinical phenotypes and poor prognosis of HCC patients. Through gain- and loss-of function experiments, we found that SATB2 significantly promoted HCC cell proliferation, migration, and invasion in vitro and HCC tumorigenicity in vivo. Furthermore, SATB2 was identified as an important regulator of stem-like properties and epithelial to mesenchymal transition (EMT) in HCC cells. In summary, our results suggested that SATB2 is a crucial upregulator of HCC, and SATB2 might be a potential prognostic marker and a therapeutic target for HCC.

[1]  Yuan Luo,et al.  SATB2 suppresses non-small cell lung cancer invasiveness by G9a , 2018, Clinical and Experimental Medicine.

[2]  Su-jin Yang,et al.  MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer. , 2016, Gene.

[3]  Y. Li,et al.  Special AT-rich sequence-binding protein 2 acts as a negative regulator of stemness in colorectal cancer cells , 2016, World journal of gastroenterology.

[4]  H. Akça,et al.  Downregulation of SATB2 is critical for induction of epithelial-to-mesenchymal transition and invasion of NSCLC cells. , 2016, Lung cancer.

[5]  S. Shankar,et al.  Role of SATB2 in human pancreatic cancer: Implications in transformation and a promising biomarker , 2016, Oncotarget.

[6]  Xianwei Mo,et al.  SATB2 suppresses gastric cancer cell proliferation and migration , 2016, Tumor Biology.

[7]  Xin Yu,et al.  miR-211 suppresses hepatocellular carcinoma by downregulating SATB2 , 2015, Oncotarget.

[8]  G. Gores,et al.  Hepatocellular carcinoma: clinical frontiers and perspectives , 2014, Gut.

[9]  Wai Leong Tam,et al.  The epigenetics of epithelial-mesenchymal plasticity in cancer , 2013, Nature Medicine.

[10]  M. Zeng,et al.  Decreased Expression of SATB2: A Novel Independent Prognostic Marker of Worse Outcome in Laryngeal Carcinoma Patients , 2012, PloS one.

[11]  R. Weinberg,et al.  Phenotypic plasticity and epithelial‐mesenchymal transitions in cancer and normal stem cells? , 2011, International journal of cancer.

[12]  Rune Thomsen,et al.  Analysis of Qpcr Data by Converting Exponentially Related CT Values into Linearly Related X0 Values , 2010, J. Bioinform. Comput. Biol..

[13]  M. Petz,et al.  Epithelial-mesenchymal transition in hepatocellular carcinoma. , 2009, Future oncology.

[14]  Jin-Lin Hou,et al.  Hepatocellular carcinoma in the Asia pacific region , 2009, Journal of gastroenterology and hepatology.

[15]  S. Byers,et al.  Liver stem cells and hepatocellular carcinoma , 2009, Hepatology.

[16]  M. Konstadoulakis,et al.  Strategies for the management of hepatocellular carcinoma , 2007, Nature Clinical Practice Oncology.

[17]  C. Paweletz,et al.  Isolation and Characterization of SATB2, a Novel AT-rich DNA Binding Protein Expressed in Development- and Cell-Specific Manner in the Rat Brain , 2006, Neurochemical Research.

[18]  D. Tarin,et al.  Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? , 2005, Cancer research.

[19]  Q. Ye,et al.  A decade’s studies on metastasis of hepatocellular carcinoma , 2004, Journal of Cancer Research and Clinical Oncology.

[20]  D. Bonthron,et al.  Identification of SATB2 as the cleft palate gene on 2q32-q33. , 2003, Human molecular genetics.

[21]  D. Woodfield Hepatocellular carcinoma. , 1986, The New Zealand medical journal.