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

Minn,Yang-Ki; Lee,Da Hye; Hyung,Woo Jin; Kim,Ji Eun; Choi,Junjeong; Yang,Seung-Ho; Song,Hotaek; Lim,Beom Jin; Kim,Se Hoon

doi:10.3892/ijo.2014.2680

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

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
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Affiliations: Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University, Seoul, Republic of Korea, Department of Pathology, Yonsei University, College of Medicine, Seoul, Republic of Korea, Department of Surgery, Yonsei University, College of Medicine, Seoul, Republic of Korea, Department of Pathology, Seoul National University, Boramae Hospital, Seoul, Republic of Korea, Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea, Department of Neurosurgery, St. Vincent Hospital, The Catholic University of Korea, Suwon, Republic of Korea, Department of Radiology and Research Institute of Radiologic Science, Yonsei University, College of Medicine, Seoul, Republic of Korea
Published online on: September 26, 2014 https://doi.org/10.3892/ijo.2014.2680
Pages: 2403-2410

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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.

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