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HOXA4-regulated miR-138 suppresses proliferation and gefitinib resistance in non-small cell lung cancer

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Abstract

Many non-small cell lung cancer (NSCLC) patients initially benefiting from gefitinib are confronted with acquired resistance. MiR-138 was previously stated as a growth inhibitor of several cancer cell lines including NSCLC cells and its expression level was significantly lower in gefitinib-resistant cells. The role of miR-138 in NSCLC cell lines PC9 and A549 was verified using methyl thiazolyl tetrazolium (MTT) assay and colony formation assay. Quantitative real-time PCR (RT-PCR) was employed to assess the level of miR-138 in gefitinib-sensitive PC9 cells and gefitinib-resistant PC9GR cells. Bioinformatic algorithms (TargetScan) and rVISTA 2.0 were used to predict binding sites on miR-138 and its target genes. MiR-138 inhibited cell proliferation of PC9 and A549 cells. In PC9GR cells, miR-138 expression was inhibited. Gefitinib treatment negatively regulated miR-138 in PC9 cells. Transfection of PC9GR cells with miR-138 mimics significantly reduced cell viability. MiR-138 was directly regulated by Homeobox A4 (HOXA4) via an HOXA4-binding site on the promoter region. TargetScan predicted numerous miR-138 target genes and EGFR was found to be the functional downstream effector of miR-138. We demonstrated that miR-138 is regulated by HOXA4 and exerts its functions via inhibiting EGFR expression in NSCLC cells.

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Authors and Affiliations

  1. Jiangxi Chest Hospital, No. 346 Dieshan Road, Nanchang, 330000, Jiangxi, China

    Xiaomei Tang

  2. Central Hospital of Wannian County, No. 168 Wansheng Avenue, Chenying, Wannian County, 335500, Jiangxi, China

    Jiying Jiang

  3. Yugan County People’s Hospital, 297 Century Avenue, Yuting, Yugan, 335100, Jiangxi, China

    Jinbao Zhu

  4. Guangdong Ascendas Genomics Technology Co., Ltd., 8th Floor South Tower, 6 Xiangxing Road, Torch Development Zone, Zhongshan, 519000, China

    Nan He

  5. ShangRao People Hospital of Jiangxi, No. 86, Shuyuan Road, Xinzhou District, Shangrao, 333100, Jiangxi, China

    Jinlong Tan

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  1. Xiaomei Tang
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  2. Jiying Jiang
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  3. Jinbao Zhu
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  4. Nan He
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  5. Jinlong Tan
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Correspondence to Jinlong Tan.

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Communicated by S. Hohmann.

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Tang, X., Jiang, J., Zhu, J. et al. HOXA4-regulated miR-138 suppresses proliferation and gefitinib resistance in non-small cell lung cancer. Mol Genet Genomics 294, 85–93 (2019). https://doi.org/10.1007/s00438-018-1489-3

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  • DOI: https://doi.org/10.1007/s00438-018-1489-3

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