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Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer

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Abstract

Brain metastasis often has a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Therefore, it is urgent to identify factors associated with lung cancer brain metastasis. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) also known as noncoding nuclear-enriched abundant transcript 2 is a long noncoding RNA, which is highly conserved amongst mammals. It has been shown to be increased in a variety of tumors including NSCLC and regulate the expression of metastasis-associated genes. However, the role of MALAT1 in lung cancer brain metastasis has not been investigated. In this study, we examined the level of MALAT1 in 78 cases of NSCLC samples with 19 brain metastasis and 59 non-brain metastasis by qRT-PCR. We observed that the level of MALAT1 was significantly higher in brain metastasis than that of non brain metastasis samples (P < 0.001). The level of MALAT1 was associated with patients’ survival. To investigate the role of MALAT1 in brain metastasis, we established a highly invasive and metastatic cell subline using the brain metastasis lung cancer cell H1915. We found that MALAT1 is increased in highly invasive subline of brain metastasis lung cancer cells. Further functional studies indicate that silencing MALAT1 inhibits highly invasive subline of brain metastasis lung cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). Therefore, increased level of long noncoding RNA MALAT1 promotes lung cancer brain metastasis by inducing EMT, which may be a promising prognosis factor and therapeutic target to treat lung cancer brain metastasis in future.

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Abbreviations

LncRNA:

Long non coding RNA

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

HOTAIR:

HOX antisense intergenic RNA

ANRIL:

Antisense noncoding RNA in the INK4 locus

NEAT2:

Noncoding nuclear-enriched abundant transcript 2

NSCLC:

Non-small cell lung cancer

EMT:

Epithelial-mesenchymal transition

ATCC:

American type culture collection

FBS:

Fetal bovine serum

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81301882, 81472366).

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Authors and Affiliations

  1. Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China

    Liqin Shen, Lei Chen & Zhixiang Zhuang

  2. Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical school of Nanjing University, Nanjing, 210008, China

    Yongsheng Wang

  3. Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, China

    Xiaochun Jiang & Hongping Xia

Authors
  1. Liqin Shen
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  2. Lei Chen
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  3. Yongsheng Wang
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  4. Xiaochun Jiang
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  5. Hongping Xia
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  6. Zhixiang Zhuang
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Corresponding authors

Correspondence to Hongping Xia or Zhixiang Zhuang.

Additional information

Liqin Shen and Lei Chen have contributed equally to this work.

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Shen, L., Chen, L., Wang, Y. et al. Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer. J Neurooncol 121, 101–108 (2015). https://doi.org/10.1007/s11060-014-1613-0

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  • DOI: https://doi.org/10.1007/s11060-014-1613-0

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