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WNT5B exerts oncogenic effects and is negatively regulated by miR-5587-3p in lung adenocarcinoma progression

Oncogene volume 39, pages 1484–1497 (2020)Cite this article

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Abstract

WNT5B glycoprotein belongs to the Wnt protein family. Limited investigations revealed a possible role of WNT5B in malignancies, such as triple-negative breast cancer and oral squamous cell carcinoma. However, whether WNT5B contributes to the progression of lung adenocarcinoma (LAD) remains unclear. Here, we initially determine that WNT5B is highly expressed in LAD and is positively correlated with lymph node metastasis and TNM stage. Consistently, clinical analysis reveals WNT5B as an independent prognostic biomarker in LAD. Silencing WNT5B suppresses the proliferation of LAD both in vitro and in vivo by interfering G1/S cell-cycle progression and modulating amino acid metabolism, revealing its remarkable oncogenic role in LAD. Of note, we also identified miR-5587-3p as a negative upstream regulator of WNT5B in LAD, which may help develop therapies targeting LAD patients with high WNT5B expression. Taken together, our results revealed an oncogenic role of WNT5B in LAD, which could be a prognostic biomarker and promising therapeutic target for LAD patients.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (grant numbers 81572937, 81572273, and 81772500); the16th batch “Summit of the Six Top Talents” Program of Jiangsu Province (grant number WSN-154); China Postdoctoral Science Foundation 12th batch Special fund (Postdoctoral number: 45786); China Postdoctoral Science Foundation 64th batch (Postdoctoral number: 45786); Jiangsu Provincial Postdoctoral Science Foundation (grant number 2018K049A); the Natural Science Foundation of Jiangsu province (grant numbers BK20180139 and BK20161386); Jiangsu Provincial Medical Youth Talent (grant number QNRC2016125), and the Nanjing Medical Science and Technology Development Project (No. ZKX17044), the Jiangsu Provincial Key Research and Development Program (No. BE2016721).

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Authors and Affiliations

  1. Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, Jiangsu, China

    Qun Zhang, Hang Fan, Suhua Zhu, Li Zhou, Hongbin Liu, Fang Zhang, Ping Zhan, Tangfeng Lv & Yong Song

  2. Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Qun Zhang

  3. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Hongda Liu

  4. Department of Respiratory Medicine, Jinling Hospital, Southern Medical University, Nanjing, 210002, Jiangsu, China

    Jiajia Jin

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Zhang, Q., Fan, H., Liu, H. et al. WNT5B exerts oncogenic effects and is negatively regulated by miR-5587-3p in lung adenocarcinoma progression. Oncogene 39, 1484–1497 (2020). https://doi.org/10.1038/s41388-019-1071-4

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