XIST promotes cell proliferation and invasion by regulating miR-140-5p and SOX4 in retinoblastoma

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.

Expressions 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.

In 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.

XIST 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.