MALAT1 regulates miR-34a expression in melanoma cells

Fei Li,Wen Liu,Li Qiao,Chengshan Xu,Xiaogang Wang,Xinji Li

doi:10.1038/s41419-019-1620-3

Fei Li, Wen Liu + Show 4 more

Open Access

https://doi.org/10.1038/s41419-019-1620-3

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Abstract

Melanoma is one of the most common skin malignancies. Both microRNAs and long non-coding RNAs (lncRNAs) have critical roles in the progression of cancers, including melanoma. However, the underlying molecular mechanism has not been fully characterized. We demonstrated that miR-34a is negatively correlated with MALAT1 in melanoma cells and tumor specimens. Interestingly, MALAT1, which contains functional sequence-specific miR-34a-binding sites, regulates miR-34a stability in melanoma cells and in vivo. Importantly, MALAT1 was significantly enriched in the Ago2 complex, but not when the MALAT1-binding site of miR-34a was mutated. Furthermore, MALAT1 could be shown to regulate c-Myc and Met expression by functioning as a miR-34a sponge. Our results reveal an unexpected mode of action for MALAT1 as an important regulator of miR-34a.

Highlights

Melanoma is an aggressive cancer involving pigmentcontaining cells known as melanocytes that are found predominantly in the skin
To investigate the potential mechanisms regulating the effects of Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on melanoma cells, we analyzed a miRNA-seq transcriptome of A375 melanoma cells transfected with MALAT1 siRNA or a scrambled control
The miR-34a expression levels in MALAT1-knockdown and control A375 cells were validated in a qRT-PCR assay, which indicated that miR-34a expression was consistent with the sequencing data (Fig. 1c)

Summary

Introduction

Melanoma is an aggressive cancer involving pigmentcontaining cells known as melanocytes that are found predominantly in the skin. Melanoma is the leading cause of skin cancer death in the United States, with an estimated 87,110 new cases and 9730 deaths in 20171. In China, it is estimated that there were 8000 new cases of melanoma and 3200 deaths due to this disease in 20152. Recent studies have revealed that non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play important roles in various pathophysiological processes, and are frequently dysregulated in many types of cancer[3,4,5,6,7,8,9]. Several studies have demonstrated that miRNAs, which regulate target mRNAs at the post-transcriptional level, are involved in the pathogenesis

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