Dataset Information

Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR

ABSTRACT: Objective: Fhit gene is known as a genome “caretaker” and frequently inactivated by deletion or hypermethylation on the promoter in several cancers. In spite of several lines of evidence, the exact mechanism underlying Fhit-induced biology is relatively less studied. This study will focus the role of Fhit in regulating Lin28 and microRNAs (miRNAs) loop. Material and Methods: To this end, we employed Fhit overexpressing isogenic cell lines to conduct miRNA nanostring array, and differentially expressed miRNAs were identified. Using real-time PCR and Western blot analysis, expression levels of Lin28b or miRNAs were investigated in response to the overexpression of Fhit gene in H1299 lung cancer cells. Results: A series of in vitro including gene nanostring analyses revealed that Lin28B protein was induced by Fhit gene overexpression, which consequently suppressed Let-7 miRNAs. Also, we found that miRNAs in miR-17/92 clusters are redundantly increased and there is an inverse correlation between Let-7 and miR-17/92 clusters in Fhit-expressing cells. Also, a series of in vitro experiments suggests that ELF-1- and/or STAT1-dependent Lin28b regulation is responsible for Let-7 induction in Fhit-expressing cancer cells. Conclusions: Based on the same experimental system proving that Fhit gene has a robust role in suppressing tumor progression and epithelial-mesenchymal transition, our data show that Fhit mediates the negative feedback between Lin28/Let-7 axis and miR-17/-92 miRNA although the physiological relevance of current interesting observation should be further investigated.

SUBMITTER: Chae H

PROVIDER: S-EPMC7797533 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveThis study aimed to report the presence of categorical and dimensional personality disorders (PD) in adults with longstanding eating disorders (ED) over a period of 17 years and to investigate whether changes in PD predict changes in ED symptoms or vice versa.MethodsIn total, 62 of the 80 living patients (78% response rate) with anorexia nervosa (n = 23), bulimia nervosa (n = 25), or other specified feeding or ED (n = 14) at baseline were evaluated during hospital treatment and at 1-year, 2-year, 5-year, and 17-year follow-up. PD were assessed using the Structured Clinical Interview for DSM-IV Axis II disorders, and the eating disorder examination (EDE) interview was used to assess ED. Data were analyzed using multilevel modeling.ResultsFrom baseline to the 17-year follow-up, the number of patients with any PD decreased significantly from 74.2% to 24.2%, and the total number of PD diagnoses declined from 80 to 22. Mean EDE score was significantly reduced from 4.2 (SD: 1.1) to 2.0 (SD: 1.6). There was a positive association between ED and PD where the initial level of either disorder was followed by similar levels of the other disorder throughout the entire follow-up period. High baseline levels of borderline PD predicted less decrease in ED symptoms. No significant within-person effects were found.ConclusionsBoth ED and PD significantly declined over time. As the severity of either disorder seems to be associated with the other, thorough assessment and treatment that incorporates both the ED psychopathology and the personality disturbances are advisable.Public significance statementWhile personality disorders were highly prevalent in the sample of patients with longstanding eating disorders, both disorders were significantly reduced at the 17-year follow-up. The disorders are related in the sense that an initial high level of either disorder is associated with a high level of the other over time. A thorough assessment and attention to both illnesses are advisable in therapy.Clinical trial identifierNCT03968705.

Project description:BackgroundResearches indicated the process of Endothelial-Mesenchymal-Transition (EndMT) of vascular endothelial cells (ECs) was critically involved in the progression of tumor. ECs demonstrated functional and phenotypic heterogeneity when located under different microenvironments. The extracellular pH of tumor tissues was acidic compared to that of normal tissues. However, there was still unclear whether the acidic microenvironment affected the EndMT of vascular ECs.MethodsHuman Umbilical Vein Endothelial Cell (HUVECs) was cultured under the normal or acidic medium to evaluate the alteration of morphology, migration, permeability, and EndMT markers. Microarray assay was adopted to analyze the differential expression of miRNAs in the acidity-treated HUVECs. Gain- and loss- of function experiments were performed to evaluate the functional role of miRNA-548ac on acidity-induced EndMT of HUVECs. Luciferase reporter and Chromatin-immunoprecipitation assays were conducted to assess the downstream pathway of miRNA-548ac in acidity-induced EndMT of HUVECs.ResultsOur results showed that HUVECs demonstrated mesenchymal transition under acidic conditions with the increase of migration, permeability, and expression of α-SMA and Vimentin, but the expression of vascular endothelial cadherin (VE-cadherin) and CD31 were reduced. In addition, the acidity-treated HUVECs remarkably facilitated the transmigration of pancreatic cancer cells. The expression of miRNA-548ac was significantly decreased in the acidity-treated HUVECs. Moreover, overexpression of miR-548ac inhibited the EndMT of HUVECs and consequently impeded the transmigration of pancreatic cancer cells. The miR-548ac inhibited the expression of YB-1 by binding to the 3'UTR of its mRNA, and YB-1 promoted the translation of Snail which was a critical regulator of EndMT. What's more, Snail transcriptionally inhibited the expression of miR-548ac through binding to the promoter of its host gene.ConclusionsOur data implicated that the acidic microenvironment promoted the EndMT of HUVECs by the miR-548ac/YB-1/Snail axis, which could contribute to the metastasis of pancreatic cancer.

Dataset Information

Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets