Background: Long noncoding RNAs (lncRNAs) are vital mediators in human cancers including pituitary neuroendocrine tumor (PitNET) and could function as competing endogenous RNAs (ceRNAs) of microRNAs (miRNAs). The main objective of this study is to identify effect of lncRNA X-inactive specific transcript (XIST) and microRNA-424-5p (miR-424-5p) on PitNET.
Methods: Microarray analysis was employed to identify the PitNET-related differentially expressed lncRNAs. PitNET tissues, including both invasive and non-invasive subtypes in parallel with normal pituitary tissues were collected for the determination of the expression of XIST, miR-424-5p and basic fibroblast growth factor (bFGF) and the interaction among them. Subsequently, the expression of XIST, miR-424-5p and bFGF in PitNET cells was altered to elucidate their biological significance in the aspects of proliferation, migration, invasion, and the apoptosis.
Results: Both XIST and bFGF exhibited high expression, but miR-424-5p had a low expression in invasive PitNET tissues as compared to non-invasive PitNET normal pituitary tissues. Additionally, XIST competitively bound to miR-424-5p to elevate the expression of bFGF. Furthermore, depleted XIST or bFGF, or elevated miR-424-5p was revealed to suppress the proliferation, migration, invasion, and promote cell cycle arrest and apoptosis of invasive PitNET cells. miR-424-5p repressed the proliferation, migration, invasion of invasive PitNET cells by targeting bFGF.
Conclusion: In conclusion, the fundamental findings of the present study suggested that the functional suppression of XIST downregulated bFGF to inhibit the development of PitNET by increasing miR-424-5p expression, proposing XIST as a novel therapeutic target for PitNET.
Keywords: invasive pituitary neuroendocrine tumor, lncRNA XIST, microRNA-424-5p, bFGF, invasion, migration