<p>LncRNA XIST depletion prevents cancer progression in invasive pituitary neuroendocrine tumor by inhibiting bFGF via upregulation of microRNA-424-5p</p>

Abstract

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.

<p>miR-424-5p Promotes Proliferation, Migration and Invasion of Laryngeal Squamous Cell Carcinoma</p>

“…Hypermethylation of the miR-424 promoter region has been reported in glioma and cervical cancer tissues, and treatment of glioma and cervical cancer cell lines with the demethylation reagent 5-aza-2ʹ-deoxycytidine increased miR-424-5p expression,31,32 so epigenetic repression by promoter region hypermethylation may be an important mechanism of downregulation of miR-424-5p in some cancers. By contrast, upregulation of miR-424-5p in cancers involves more complex transcriptional and post-transcriptional mechanisms, such as dysregulated upstream transcription factors and long non-coding RNA 33–35…”

The Search of miRNA Related to Invasive Growth of Nonfunctioning Gonadotropic Pituitary Tumors

“…We conclude that our results suggest the lack of universal miRNA profile of the tumor that determines invasive growth. It does not imply that expression of particular miRNA does not play a role in the aggressive phenotype of nonfunctioning pituitary tumors, as shown by some previous functional experiments [ 24 , 25 , 43 ]. We would rather assume that different mechanisms and various molecular changes may contribute to the acquisition of ability of infiltrative growth.…”

Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells

“…These target genes generally exert a protumor activity by promoting proliferation, migration, or angiogenesis in cancer cells. A few lncRNAs have been found to regulate miR-424-5p in various cancer cells, including LINC00922 in breast cancer [ 39 ], CDNK2B-AS1 in hepatocellular carcinoma [ 40 ], and XIST in neuroendocrine tumors [ 41 ]. In all the aforementioned cases, regulation of miR-424-5p by the corresponding lncRNA resulted in cell proliferation or cancer-progression alterations.…”