WNT5B exerts oncogenic effects and is negatively regulated by miR-5587-3p in lung adenocarcinoma progression
WNT5B exerts oncogenic effects and is negatively regulated by miR-5587-3p in lung adenocarcinoma progression
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WNT5B 在肺腺癌进展中发挥致癌作用并受到 miR-5587-3p 的负向调节
DOI：
10.1038/s41388-019-1071-4
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发表时间：
2020-02-01
期刊：
影响因子：
8
通讯作者：
Song, Yong
中科院分区：
文献类型：
--
作者：
Zhang, Qun;Fan, Hang;Song, Yong
WNT5B糖蛋白属于WNT蛋白家族。有限的研究揭示了WNT5B在恶性肿瘤中的可能作用，例如三阴性乳腺癌和口腔鳞状细胞癌。然而，WNT5B是否与肺腺癌(LAD)的进展有关尚不清楚。在此，我们初步确定WNT5B在LAD中高表达，并与淋巴结转移和TNM分期呈正相关。临床分析一致显示WNT5B是LAD的独立预后生物标志物。沉默WNT5B通过干扰G1/S细胞周期进程和调节氨基酸代谢抑制LAD的体外和体内增殖，显示其在LAD中的显著致癌作用。值得注意的是，我们还发现miR-5587-3p是LAD中WNT5B的负上游调节因子，这可能有助于开发针对WNT5B高表达的LAD患者的治疗。综上所述，我们的结果揭示了WNT5B在LAD中的致癌作用，它可能是LAD患者预后的生物标志物和有前途的治疗靶点。
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.