MALAT1 promoted invasiveness of gastric adenocarcinoma

Na Keum Lee, Jung Hwa Lee, Cristina Ivan, Hui Ling, Xinna Zhang, Chan Hyuk Park, George A. Calin, SangKil Lee

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Abstract

Background: Gastric cancer is the second leading cause of cancer globally, and the mechanism of its pathogenesis is still largely unknown. Recently, non-coding RNAs have been recognized to promote metastasis in various cancers, including gastric cancer. Methods: We found that metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is upregulated in gastric cancer tissue compared to adjacent normal tissue, as determined by microarray and subsequent qRT-PCR, then investigated the impact of MALAT1 on apoptosis, cell proliferation, and the cell cycle to dissect the carcinogenesis of gastric cancer, and examined mechanisms of invasion and metastasis. Expression of MALAT1 and U6 was determined by SYBR qRT-PCR in nine-teen gastric cancer cell lines and fifty fresh samples of cancer tissue and adjacent tissues. Downregulation of MALAT1 was accomplished with two different siRNAs. Cell proliferation was determined after treatment with these siRNAs. FACS using PI/Annexin-V staining was carried out. To analyze the invasiveness, a scratch wound-healing assay and a Matrigel invasion assay were performed. Cancer related gene expression assay was done after transfection of siR- MALAT1. Results: The expression of MALAT1 was significantly elevated in various gastric cancer cell lines and gastric cancer tissues compared to normal cell lines and tissues (p < 0.01). siR-MALAT1 significantly reduced viable AGS cell numbers and induced apoptosis (p < 0.05). Deep invasion of tumor (advanced T stages) was more common in the high MALAT1-level group (p = 0.039). siR-MALAT1 significantly decreased AGS cell invasiveness and migration. siR-MALAT1 reduced expression of snail and N-cadherin, and elevated E-cadherin. The Wnt/β-catenin related genes were significantly decreased by transfection of siRNA MALAT1. MALAT1 is involved in gastric carcinogenesis via inhibition of apoptosis and promotes invasiveness via the epithelial-to-mesenchymal transition. Conclusions: In our study, we found that deregulation of MALAT1 could be involved in both tumorigenesis and invasiveness in gastric cancer cells.

Original languageEnglish
Article number46
JournalBMC Cancer
Volume17
Issue number1
DOIs
Publication statusPublished - 2017 Jan 11

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Lee, N. K., Lee, J. H., Ivan, C., Ling, H., Zhang, X., Park, C. H., Calin, G. A., & Lee, S. (2017). MALAT1 promoted invasiveness of gastric adenocarcinoma. BMC Cancer, 17(1), [46]. https://doi.org/10.1186/s12885-016-2988-4