Abstract
Melanoma is the most malignant skin cancer, which account for most of skin-cancer-related deaths. Long noncoding RNA (lncRNA) is a class of noncoding RNAs with crucial roles in many cancers. However, the roles of lncRNAs in melanoma have not been well studied. In the present study, using public available data and clinical tissues samples, we found that lncRNA ILF3-AS1 is up-regulated in melanoma tissues and cell lines, and correlated with poor prognosis of melanoma patients. Functional experiments showed that knockdown of ILF3-AS1 inhibits melanoma cell proliferation, migration, and invasion. Mechanistically, we found that ILF3-AS1 interacts with EZH2, promotes the binding of EZH2 to the miR-200b/a/429 promoter, and represses miR-200b/a/429 expression. The expression of ILF3-AS1 is negatively correlated with that of miR-200b/a/429 in melanoma tissues. Moreover, inhibition of miR-200b/a/429 abrogates the biological roles of ILF3-AS1 knockdown on melanoma cell proliferation, migration, and invasion. In conclusion, these results demonstrate that melanoma-upregulated lncRNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429, and imply that ILF3-AS1 may be a potential prognostic biomarker and therapeutic target for melanoma.
Highlights
Derived from malignant transformation of melanocytes, melanoma is the most aggressive skin cancer, which accounts for 75% of all skin-cancer-related deaths [1,2]
To investigate the expression of ILF3-AS1 in melanoma, we first searched the MiTranscriptome database [8], and found that ILF3-AS1 is increased in primary melanomas and metastatic melanomas compared with normal human melanocytes (NHMEs) (Figure 1A)
Patients with higher ILF3-AS1 expression had a worse overall survival than those with lower ILF3-AS1 expression. These results showed that ILF3-AS1 is up-regulated in melanoma tissues and high ILF3-AS1 expression is correlated with metastatic characteristic and poor prognosis
Summary
Derived from malignant transformation of melanocytes, melanoma is the most aggressive skin cancer, which accounts for 75% of all skin-cancer-related deaths [1,2]. Despite recent advances in molecularly targeted therapy and immunotherapy, melanoma rapidly develops resistance to these therapies [4,5,6]. With great advances of high-throughput RNA sequencing technology, many reports have shown that most of human transcriptome could be classified as long noncoding RNAs (lncRNAs) [8,9]. Accumulating evidence demonstrate that lncRNAs play important roles in tissue physiology and diseases processes, including cancers [12,13,14,15,16]. Many lncRNAs show aberrant expressions in a variety of cancers, and some dysregulated lncRNAs function as oncogenes or tumor suppressors in particular conditions [17,18,19]. The functions and action mechanisms of lncRNAs in melanoma are still poorly understood [20]
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