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microRNA-590 suppresses the tumorigenesis and invasiveness of non-small cell lung cancer cells by targeting ADAM9

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Abstract

microRNAs (miRNAs), a family of small non-coding RNA molecules, are implicated in cancer growth and progression. In the present study, we examined the expression and biological roles of miR-590 in non-small cell lung cancer (NSCLC). Compared to normal lung tissues, miR-590 expression was downregulated in primary NSCLCs and, to a greater extent, in corresponding brain metastases. NSCLC cell lines with high metastatic potential had significantly (P < 0.05) lower levels of miR-590 than those with low metastatic potential. Re-expression of miR-590 suppressed NSCLC cell proliferation, colony formation, migration, and invasion in vitro and tumorigenesis in vivo. In contrast, inhibition of miR-590 enhanced the migration and invasion of NSCLC cells. Mechanistic studies revealed that a disintegrin and metalloproteinase 9 (ADAM9) was a direct target of miR-590. Delivery of miR-590 mimic was found to decrease endogenous ADAM9 expression in NSCLC cells. Enforced expression of a miRNA-resistant form of ADAM9 significantly restored the aggressive behaviors in miR-590-overexpressing NSCLC cells. Taken together, our data reveal miR-590 as a tumor suppressor in NSCLC, which is at least partially mediated through targeting of ADAM9. Restoration of miR-590 may provide a promising therapeutic strategy for NSCLC.

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    Authors and Affiliations

    1. Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

      Fei-fei Wang & Jing-liang Cheng

    2. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

      Song Wang & Wen-hua Xue

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    1. Fei-fei Wang
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    2. Song Wang
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    3. Wen-hua Xue
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    4. Jing-liang Cheng
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    Correspondence to Jing-liang Cheng.

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    Fei-fei Wang and Song Wang have contributed equally to this work.

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    Wang, Ff., Wang, S., Xue, Wh. et al. microRNA-590 suppresses the tumorigenesis and invasiveness of non-small cell lung cancer cells by targeting ADAM9. Mol Cell Biochem 423, 29–37 (2016). https://doi.org/10.1007/s11010-016-2822-y

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    • DOI: https://doi.org/10.1007/s11010-016-2822-y

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