MicroRNA-200 family members and ZEB2 are associated with brain metastasis in gastric adenocarcinoma.

Abstract

Although the incidence of brain metastasis in gastric cancer is relatively low, its prevalence may increase with improved therapy and longer survival tumors. The molecular mechanisms underlying brain metastases are not well understood. To gain insight into the mechanism of brain metastasis, we studied differences in microRNA (miRNA) expression levels in 8 cases of matched primary gastric adenocarcinoma and brain metastatic adenocarcinoma using the Illumina microRNA microarray chip. We identified 6 upregulated and 2 downregulated miRNAs in all 8 cases simultaneously. Interestingly, 2 out of 8 miRNAs (hsa-miR‑141-3p and hsa-miR-200b-3p) belonged to the miR-200 family. Online microRNA database searching revealed that ZEB2 is the top-ranked target gene for hsa-miR141-3p and hsa-miR-200b-3p, prompting us to focus ZEB2 expression in brain metastatic adenocarcinoma. We confirmed that ZEB2 expression was markedly downregulated in some brain metastatic samples. In addition, decreased ZEB2 expression was noted by western blot analysis of 2 metastatic gastric adenocarcinoma cell types that were derived by in vivo selection following intracardiac injection of gastric cancer cell lines. In conclusion, we demonstrate that expression of miRNA-200 family members and ZEB2 are associated with brain metastases of gastric adenocarcinoma, not only in matched patient samples, but also in metastatic cell lines that were derived by in vivo selection.

• Authors: Yang-Ki Minn, Da Hye Lee, Woo Jin Hyung, Ji Eun Kim, Junjeong Choi, Seung-Ho Yang, Hotaek Song, Beom Jin Lim, Se Hoon Kim
• Journal: International journal of oncology (Int J Oncol) Vol. 45 Issue 6 Pg. 2403-10 (Dec 2014) ISSN: 1791-2423 [Electronic] Greece
• PMID: 25270520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Homeodomain Proteins
• MIRN200 microRNA, human
• MicroRNAs
• Repressor Proteins
• ZEB2 protein, human
• Zinc Finger E-box Binding Homeobox 2

Topics

• Adenocarcinoma (genetics, pathology)
• Animals
• Brain Neoplasms (genetics, pathology, secondary)
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Homeodomain Proteins (biosynthesis, genetics)
• Humans
• Lymphatic Metastasis
• Male
• Mice
• MicroRNAs (biosynthesis, genetics)
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Repressor Proteins (biosynthesis, genetics)
• Stomach Neoplasms (genetics, pathology)
• Zinc Finger E-box Binding Homeobox 2