LncRNA UCA1-miR-507-FOXM1 axis is involved in cell proliferation, invasion and G0/G1 cell cycle arrest in melanoma

Abstract

Recently, the incidence of melanoma has been on the rise. Patients with distant metastasis share poor prognosis. Increasing studies have been conducted to clarify the molecular mechanisms as well as to investigate potential effective therapeutic targets in the development of melanoma. This study focuses on the LncRNA UCA1 and its downstream regulated factors. In our experiments, UCA1 expression was discovered to be upregulated in melanoma tissues and cells, while the depletion of UCA1 led to the inhibition of cell proliferation, invasion and cell cycle arrest. To further our understanding of the mechanisms of UCA1, a system of experiments was built. We found that miR-507 could directly bind to UCA1 at the miRNA recognition site, and that there was a negative correlation between miR-507 and UCA1. Additionally, FOXM1 is a target of miR-507 and can be downregulated by either miR-507 overexpression or UCA1 depletion. Downregulated FOXM1 was analogous to the depletion of UCA1 and the overexpression of miR-507. These results, taken together, provide evidence for a novel UCA1 interaction regulatory network in tumorigenesis of melanoma.

Long non-coding RNAs in cutaneous melanoma: clinical perspectives

“…[61] In melanoma, UCA1 was found to be upregulated in both primary and metastatic melanoma samples. [62, 63] UCA1 is believed to exert its oncogenic functions by acting as a miRNA sponge for miR-507. As a result, FOXM1, a target of miR-507, is downregulated upon UCA1 depletion in melanoma cell lines, resulting in the inhibition of cell proliferation.…”

“…As a result, FOXM1, a target of miR-507, is downregulated upon UCA1 depletion in melanoma cell lines, resulting in the inhibition of cell proliferation. [63]…”

“…MALAT1 [62] and UCA1 [63] are upregulated in melanoma and both may indicate lymph node metastasis in melanoma. The expression of MALAT1 in 63 lymph node metastatic tissue samples was higher than in paired primary melanomas.…”

Function and Clinical Implications of Long Non-Coding RNAs in Melanoma

“…A study comparing the expression of six cancer-implicated lncRNAs in melanoma to their respective expression in paired adjacent healthy tissue, found elevated expression of UCA1 in melanoma, especially at advanced stages [109,125]. Knockdown of UCA1 inhibited melanoma cell migration suggest that it might be involved in tumor dissemination [109].…”

“…In fact, UCA1 might act as a decoy lncRNA targeting miR-507, an inhibitor of the pro-oncogenic transcription factor FoxM1 (Figure 1A). Depletion of UCA1 increased the levels of miR-507 and reduced FoxM1 levels which led to cell cycle progression defects [125]. In turn, this led to decreased cell proliferation through G1 cell cycle arrest (functionally summarized in Table 1).…”