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miR-30a-5p enhances paclitaxel sensitivity in non-small cell lung cancer through targeting BCL-2 expression

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Abstract

Lung cancer remains the leading cause of cancer-related death worldwide. Paclitaxel, either as monotherapy or combined with other agents, is the standard treatment for advanced non-small cell lung cancer (NSCLC), the most common type of lung cancer. However, both de novo and acquired resistance against paclitaxel frequently occurs and represents a huge clinical problem. The underlying mechanisms remain poorly characterized. Here, by comparing microRNA (miRNA) expression levels using miRNA arrays, we observed differential expression of miR-30a-5p in two independent lung cancer cell pairs (paclitaxel-resistant vs paclitaxel-sensitive A549 cell lines). Overexpression of miR-30a-5p sensitizes NSCLC cells to paclitaxel both in vitro and in vivo. In addition, miR-30a-5p increases paclitaxel sensitivity by promoting chemotherapy-induced apoptosis via downregulating BCL-2, a key apoptosis regulator. High miR-30a-5p expression is positively correlated with enhanced responsiveness to paclitaxel and predicts a more favorable clinical outcome in NSCLC patients. Moreover, miR-30a-5p expression is negatively correlated with BCL-2 expression in NSCLC tissues. These data indicate that miR-30a-5p may be useful to treat paclitaxel-resistant lung cancer and may also provide a biomarker to predict paclitaxel responsiveness in lung cancer.

Key messages

  • BCL-2 is a novel direct target of miR-30a-5p.

  • miR-30a-5p enhances NSCLC paclitaxel sensitivity in vitro and in vivo.

  • miR-30a-5p sensitizes NSCLC cells to paclitaxel by inducing apoptosis through BCL-2 inhibition.

  • miR-30a-5p negatively correlates with BCL-2 and predicts a favorable clinical outcome in NSCLC patients.

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Acknowledgements

This work was supported by the National Natural Science Foundation (81330053, 81372161, 81472589, 81630067, 81672602, 81502264, and 81572597) and Beijing Nova Program (Z141102001814055). Beijing Institute of Biotechnology and PLA General Hospital contribute to this work equally.

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Author notes

  1. Xiaojie Xu, Shuai Jin, Yongfu Ma, and Zhongyi Fan contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China

    Xiaojie Xu, Ling Li & Qinong Ye

  2. Department of Thoracic surgery, PLA General Hospital, Beijing, China

    Shuai Jin, Yongfu Ma & Yang Liu

  3. Department of Oncology, PLA General Hospital, Beijing, China

    Zhongyi Fan

  4. Department of Gynecology and Obstetrics, PLA General Hospital, Beijing, 100853, China

    Zhifeng Yan, Qi Song, Wenye You & Ying Li

  5. Department of Paediatric Orthopaedic Surgery, PLA General Hospital, Beijing, China

    Wenchao Li

  6. Department of Endocrinology and Metabolism, PLA General Hospital, Beijing, China

    Zhaohui Lyu, Yeqiong Song & Pingan Shi

  7. Department of Ophthalmology, The First Affiliated Hospital of Jinzhou Medical University, Beijing, China

    Ying Liu & Xiao Han

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  1. Xiaojie Xu
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Correspondence to Ying Li, Yang Liu or Qinong Ye.

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Xu, X., Jin, S., Ma, Y. et al. miR-30a-5p enhances paclitaxel sensitivity in non-small cell lung cancer through targeting BCL-2 expression. J Mol Med 95, 861–871 (2017). https://doi.org/10.1007/s00109-017-1539-z

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  • DOI: https://doi.org/10.1007/s00109-017-1539-z

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