MiR-4458/human antigen R (HuR) modulates PBX3 mRNA stability in melanoma tumorigenesis
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ORIGINAL PAPER
MiR‑4458/human antigen R (HuR) modulates PBX3 mRNA stability in melanoma tumorigenesis Henghua Zhou1 · Yamin Rao1 · Qilin Sun2 · Yang Liu2 · Xiaobo Zhou2 · Ying Chen1 · Jun Chen2 Received: 26 July 2019 / Revised: 11 February 2020 / Accepted: 12 February 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords miR-4458 · HuR · PBX3 · Melanoma
Introduction Melanoma, a fatal skin malignancy, is considered as the 5th and 6th most common cancer in men and women, respectively, in the United States and ranks the 15th among most common cancers worldwide [1–3]. It is a highly aggressive Henghua Zhou and Yamin Rao contributed equally to this work. * Ying Chen [email protected] * Jun Chen [email protected] 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
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
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tumor with an increasing incidence [4–6]. Thus, it would be of significance to delve into the relevant molecular mechanisms, which might be helpful for explaining the tumorigenesis and development of melanoma. MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs with 19–25 nucleotides, which typically obstruct translation and stability of target mRNAs expression via binding to the 3′-untranslated regions (3′UTR) [7]. Surging evidence has uncovered
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