ABSTRACT
MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression by sequence-specifically targeting multiple mRNAs. Although miR-33a was recently reported to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are largely unknown. Here, we found that downregulated miR-33a in breast cancer tissues correlates with lymph node metastasis. MiR-33a expression is significantly lower in the highly metastatic breast cancer cell lines than the noncancerous breast epithelial cells and non-metastatic breast cancer cells. Moreover, the overexpression of miR-33a in metastatic breast cancer cells remarkably decreases cell proliferation and invasion in vitro and significantly inhibits tumor growth and lung metastasis in vivo, whereas its knockdown in non-metastatic breast cancer cells significantly enhances cell proliferation and invasion in vitro and promotes tumor growth and lung metastasis in vivo. Combining bioinformatics prediction and biochemical analyses, we showed that ADAM9 and ROS1 are direct downstream targets of miR-33a. These findings identified miR-33a as a negative regulator of breast cancer cell proliferation and metastasis.
Subject(s)
Animals , Female , Humans , Mice , Middle Aged , ADAM Proteins , Genetics , Breast Neoplasms , Genetics , Pathology , Cell Line, Tumor , Cell Movement , Genetics , Cell Proliferation , Genetics , Lung Neoplasms , Membrane Proteins , Genetics , MicroRNAs , Genetics , Neoplasm Invasiveness , Neoplasm Metastasis , Protein-Tyrosine Kinases , Genetics , Proto-Oncogene Proteins , GeneticsABSTRACT
Background and purpose:Differentiation of tumor tissue is an important factor on determining the prognosis of gastric cancer. This study aimed to investigate the expression levels and clinical signiifcance of gender determining region Y-box 2 (SOX2) gene and octamer binding factor 4 (OCT4) gene in gastric cancer tissues varying different differentiation degrees. Methods: Sixty cases with gastric cancer were recruited in this study. The gastric cancer tissues and corresponding normal mucosa of the 60 cases were obtained. The mRNA and protein level of SOX2, OCT4 gene are evaluated by the quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry, respectively. The relationship between the expression levels of SOX2, OCT4 gene and clinical pathological parameters were also analyzed in this study. Results:The expression of SOX2 in both mRNA and protein levels had no signiifcant difference between the well-differentiated gastric cancer tissues and normal gastric mucosa (mRNA levels:t=0.1033, P>0.05;protein levels:t=0.116, P>0.05). However, both the mRNA and protein expression of SOX2 in patients with well-differentiated gastric cancer tissues were signiifcant higher than not only in patients with moderately differentiated gastric carcinoma (mRNA levels: t=12.48, P0.05;protein levels:t=1.064, P>0.05). Immunohistochemical study demonstrated that the positive rate of SOX2 in patients with well-differentiated gastric cancer tissues (10/21) were higher than in patients with not only moderately differentiated gastric carcinoma (7/20) but also poorly differentiated gastric carcinoma (2/19, P0.05). Nevertheless, the expression of SOX2, OCT4 were positive or negative correlated with the pathological staging, the degree of inifltration and lymph node metastasis (P<0.05). Conclusion:Decreased SOX2 expression and increased expression level of OCT4 can promote the formation, development and invasion of gastric cancer and they may become biomarkers or the diagnosis, treatment and prognosis evaluation in gastric carcinoma.