Abstract
BackgroundRetinoblastoma (RB) is the most common intraocular malignancy in children. Long non-coding RNA X-inactive specific transcript (lncRNA XIST) has been reported to be associated with RB, but research on the mechanism of XIST is not well studied.MethodsExpressions of XIST, microRNA-140-5p (miR-140-5p), and sex-determining region Y-related high-mobility group box 4 (SOX4) were analyzed by qRT-PCR or Western blot. Relationships of XIST, SOX4, and miR-140-5p were evaluated by dual-luciferase reporter assay and Spearman’s analysis. Cell Counting Kit-8 (CCK-8) and Transwell assay were performed to assess the function of XIST on RB cell proliferation and invasion.ResultsIn RB tissues, XIST and SOX4 expressions were obviously increased, but the miR-140-5p expression was markedly reduced. XIST expression was positively related to SOX4 expression while negatively correlated with miR-140-5p expression, and negative correlation was exhibited between miR-140-5p and SOX4 expression in RB tissues. XIST was confirmed to directly bind to miR-140-5p, and SOX4 was one target of miR-140-5p. XIST knockdown could impede RB cell proliferation and invasion, while miR-140-5p inhibition reversed the effects. In addition, XIST overexpression or miR-140-5p inhibition could abrogate the inhibition of SOX4 silencing on cell proliferation and invasion of RB cells.ConclusionsXIST was obviously increased in RB tissues and cells, and XIST inhibition repressed the proliferation and invasion of RB cells by miR-140-5p/SOX4 axis, which may provide new understandings of the XIST molecular mechanism in RB.
Highlights
Retinoblastoma (RB) is the most common intraocular malignancy in children
We found that Xinactive specific transcript (XIST) and sex-determining region Y-related high-mobility group box 4 (SOX4) expressions were increased while miR-140-5p was decreased both in RB tissues and cells
XIST expression was increased in RB tissues and cells Firstly, we analyzed the XIST expression in RB tissues and found XIST expression was obviously increased in RB tissues versus normal tissues (Fig. 1a)
Summary
Retinoblastoma (RB) is the most common intraocular malignancy in children. Long non-coding RNA X-inactive specific transcript (lncRNA XIST) has been reported to be associated with RB, but research on the mechanism of XIST is not well studied. Retinoblastoma (RB) is the most common intraocular malignancy in children and rare in adults, with poor prognosis, which seriously affects the vision of children and even endangers life [1]. The study of Zhang et al suggested that H19 was a decreased expression and suppressed RB progression [7], while Li et al found that H19 was upregulated in RB and may act as an oncogenic function in RB progression [8]. Xinactive specific transcript (XIST), a widely studied lncRNA, has been reported that it was dysregulated and functioned as an oncogene in RB [9, 10]. Our knowledge about detailed mechanisms for XIST in RB is still insufficient
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