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MiR-4458/human antigen R (HuR) modulates PBX3 mRNA stability in melanoma tumorigenesis

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Abstract

Melanoma, a malignancy of the melanocyte, is characterized as the most fatal skin cancer with an increasing incidence. Of note, in spite of great attempts made for better treatment, the therapeutic outcome is barely satisfactory. Abnormal expression of microRNAs (miRNAs) acting as oncogenes or tumor suppressor genes, is frequently implicated in multiple human cancers, including melanoma. Here, we found that miRNA-4458, a reportedly tumor-suppressive miRNA in several cancers, was downregulated in melanoma cells. Besides, our findings indicated that microRNA-4458 (miR-4458) hindered cell proliferation and migration, yet induced apoptosis in melanoma. Mechanical interaction of miR-4458 and PBX3 mRNA, thereby inhibiting PBX3 expression in melanoma cells, was also presented in this work. Human antigen R (HuR) was reported to be greatly upregulated in diverse cancers and HuR-dependent stabilization of target gene contributed a lot to tumor progression. In this study, it revealed the stabilization of PBX3 mRNA by HuR, thereby boosting PBX3 expression. Lastly, we concluded that miR-4458 and HuR modulated the expression of PBX3 in a competitive manner in melanoma tumorigenesis, which might yield a novel insight into the molecular pathogenesis of melanoma.

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Acknowledgements

This study was supported by the Fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai JiaoTong University School of Medicine (no. JYZZ009) and Fundamental research of Star project of Shanghai JiaoTong University (no. YG2019QNB13).

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  1. Henghua Zhou and Yamin Rao contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Shanghai Ninth People’s Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Center for Specialty Strategy Research of Shanghai JiaoTong University China Hospital Development Institute, Shanghai, 200011, China

    Henghua Zhou, Yamin Rao & Ying Chen

  2. Department of Dermatology and Dermatologic Surgery, Shanghai Ninth People’s Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Center for Specialty Strategy Research of Shanghai JiaoTong University China Hospital Development Institute, No. 639 Zhizaoju Road, Shanghai, 200011, China

    Qilin Sun, Yang Liu, Xiaobo Zhou & Jun Chen

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  1. Henghua Zhou
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Zhou, H., Rao, Y., Sun, Q. et al. MiR-4458/human antigen R (HuR) modulates PBX3 mRNA stability in melanoma tumorigenesis. Arch Dermatol Res 312, 665–673 (2020). https://doi.org/10.1007/s00403-020-02051-8

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  • DOI: https://doi.org/10.1007/s00403-020-02051-8

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