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

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.

SUBMITTER: Zhou K

PROVIDER: S-EPMC6730611 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Zhou Kai K Li Shaoshan S Du Guojia G Fan Yandong Y Wu Pengfei P Sun Hongjie H Zhang Tingrong T

OncoTargets and therapy 20190902

<h4>Background</h4>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.<h4>Methods</h4>Microarray analysis was employed to identify the PitNET-related differentially expressed lncRNAs. PitNET tissues, includin ...[more]

PMID: 31564894

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Project description:Background and aimAbout a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates.MethodsWe performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas' classification as primary outcomes. Secondary outcomes included the TPS' relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis.ResultsEighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas' classification, we found that "proliferative" cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80-18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98-14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10-0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence.ConclusionsPD-L1 expression was associated with proliferative grades of Trouillas' classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.

Project description:BackgroundNeuroinflammation is a common feature of many neurological diseases, and remains crucial for disease progression and prognosis. Activation of microglia and astrocytes can lead to neuroinflammation. However, little is known about the role of lncRNA xist and miR-122-5p in the pathogenesis of sepsis-associated neuroinflammation (SAN). This study aims to investigate the role of lncRNA xist and miR-122-5p in the pathogenesis of SAN.MethodsLevels of miR-122-5p and proinflammatory mediators were detected in the cerebrospinal fluid (CSF) of patients with intracranial infection (ICI) by ELISA and qRT-PCR. miRNA expression in the periventricular white matter (PWM) in rats was analyzed by high-throughput sequencing. Levels of lncRNA xist, miR-122-5p and proinflammatory mediators in the PWM were measured using qRT-PCR and western blot. Bioinformatics analysis was used to predict the upstream and downstream of miR-122-5p. The interaction between miR-122-5p and its target protein was validated using luciferase reporter assay. BV2 and astrocytes were used to detect the expression of lncRNA xist, miR-122-5p.ResultsThe level of miR-122-5p was significantly decreased in the CSF of ICI patients, while the expression of IL-1β and TNF-α were significantly upregulated. Furthermore, it was found that the expression of IL-1β and TNF-α were negatively correlated with the level of miR-122-5p. A high-throughput sequencing analysis showed that miR-122-5p expression was downregulated with 1.5-fold changes in the PWM of CLP rats compared with sham group. Bioinformatics analysis found that lncRNA xist and PKCη were the upstream and downstream target genes of miR-122-5p, respectively. The identified lncRNA xist and PKCη were significantly increased in the PWM of CLP rats. Overexpression of miR-122-5p or knockdown of lncRNA xist could significantly downregulate the level of PKCη and proinflammatory mediators from activated microglia and astrocytes. Meanwhile, in vitro investigation showed that silencing lncRNA xist or PKCη or enhancing the expression of miR-122-5p could obviously inhibit the release of proinflammatory mediators in activated BV2 cells and astrocytes.ConclusionLncRNA xist could regulate microglia and astrocytes activation in the PWM of CLP rats via miR-122-5p/PKCη axis, further mediating sepsis associated neuroinflammation.

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

Publications

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

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