scholarly journals The Severity of Muscle Performance Deterioration in Sarcopenia Correlates With Circulating Muscle Tissue-Specific miRNAs

2021 ◽  
pp. S91-S98
Author(s):  
S. Valášková ◽  
A. Gažová ◽  
P. Vrbová ◽  
T. Koller ◽  
B. Šalingová ◽  
...  

Sarcopenia is defined as an age-associated loss of skeletal muscle function and muscle mass and is common in older adults. Sarcopenia as a disease is currently of interest not only to orthopedists and surgeons but also to internists, endocrinologists, rheumatologists, cardiologists, diabetologists, gynaecologists, geriatricians and paediatricians. In cooperation with the 5th Internal Medicine Clinic, we, as a unit of clinical research, aimed to describe a sarcopenic specific miRNA expression profile for disease diagnostics and classification of the severity of muscle performance deterioration. This study included a total of 80 patients (age 55-86 years) hospitalized at the V. Internal medicine clinic of LFUK and UNB with different severity of muscle performance deterioration. The study participants were evaluated and classified according to short physical performance battery score (SPPB). In this study, we investigated the role of circulating miRNAs in sarcopenia in the elderly. We hypothesized that sarcopenia effects the expression of muscle tissue-specific miRNAs (MyomiRNAs), which could be potentially reflected in the blood plasma miRNA expression profile. The expression of specific circulating miRNAs in patients with different muscle performances was analyzed. Patients’ blood plasma was evaluated for the expression of myomiRNAs: miRNA-29a, miRNA-29b, miRNA-1, miRNA-133a, miRNA-133b, miRNA-206, miRNA-208b and miRNA-499, and the data were correlated with diagnostic indicators of the disease. We showed a specific sarcopenia miRNA profile that could be considered a possible biomarker for the disease. Patients with low muscle performance showed increased miRNA-1, miRNA-29a and miRNA-29b expression and decreased for the miRNA-206, miRNA-133a, miRNA-133b, miRNA-208b and miRNA-499 expression. We show that the severity of muscle performance deterioration in sarcopenia correlates with specific miRNA expression. We also propose the profile of miRNAs expression in blood plasma as a specific biomarker for sarcopenia diagnostics. Future clinical studies will be necessary to eventually naturally have to elucidate the underlined molecular mechanism responsible for specific miRNAs expression in sarcopenia pathology and progression of the disease.

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Yazmín Gómez-Gómez ◽  
Jorge Organista-Nava ◽  
Patricio Gariglio

MicroRNAs (miRNAs) are a class of small non coding RNAs of 18–25 nucleotides in length. The temporal or short-lived expression of the miRNAs modulates gene expression post transcriptionally. Studies have revealed that miRNAs deregulation correlates and is involved with the initiation and progression of human tumors. Cervical cancer (CC) displays notably increased or decreased expression of a large number of cellular oncogenic or tumor suppressive miRNAs, respectively. However, understanding the potential role of miRNAs in CC is still limited. In CC, the high-risk human papillomaviruses (HR-HPVs) infection can affect the miRNAs expression through oncoprotein E6 and E7 that contribute to viral pathogenesis, although other viral proteins might also be involved. This deregulation in the miRNAs expression has an important role in the hallmarks of CC. Interestingly, the miRNA expression profile in CC can discriminate between normal and tumor tissue and the extraordinary stability of miRNAs makes it suitable to serve as diagnostic and prognostic biomarkers of cancer. In this review, we will summarize the role of the HR-HPVs in miRNA expression, the role of miRNAs in the hallmarks of CC, and the use of miRNAs as potential prognostic biomarkers in CC.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 311-311
Author(s):  
Cristiana Carniti ◽  
Silvia Gimondi ◽  
Davide Lucini ◽  
Jacopo Mariotti ◽  
Anisa Bermema ◽  
...  

Abstract Abstract 311 Background: Acute graft-versus-host disease (aGVHD) results in significant morbidity and mortality and remains the main complication of alloHSCT. Noninvasive, diagnostic and prognostic tests for aGVHD are currently lacking but essential to predict GVHD and to improve the safety and accessibility of alloHSCT. We hypothesized that the prospective analysis of miRNA expression profile in the plasma of allografted patients could allow for the detection of specific miRNAs with predictive role for aGVHD. Methods: After informed consent, we collected plasma samples from 10 healthy donors and 22 patients (median age: 59 and 41 years) who received unmanipulated alloHSCT (18 from Matched Unrelated Donors and 4 from HLA-matched siblings). Blood samples were collected weekly after HSCT and patients were monitored to assess aGVHD onset. MicroRNAs were isolated from the plasma and the miRNA expression profile examined using a quantitative PCR-method (TaqMan® Human microRNA Cards, Applied Biosystems). The results obtained were subsequently validated with specific miRNA Single Assays (Applied Biosystems). To verify whether the miRNAs emerged from the human studies represent markers of aGVHD and provide information regarding the involvement of specific target organs, a major histocompatibility complex (MHC) mismatched HSCT mouse model was used. Recipient BALB/c mice were lethally irradiated and treated either with spleen and bone marrow (BM) cells from C57BL/6 (B6) donors (GVHD cohort, n=22) or with BM cells only (negative control, n=18). Syngeneic transplants (B6àB6, n=6 were also included. Mice were characterized for GVHD onset by monitoring overall survival and weight loss. Recipient mice were sacrificed and tissues harvested on day 9, 14 and 18 post transplant and GVHD confirmed by histology and scored according to Foley et al, 2008. MiRNAs expression profile have been characterized in the plasma, skin, liver, colon and lymphocytes of GVHD and non-GVHD control cohorts Results: Three of 22 patients developed intestinal GVHD (grade 2) and 9 of 22 patients developed cutaneous GVHD (grade 2–3). By comparing the circulating miRNAs expression profiles of GVHD patients and non GVHD patients, we identified a group of 8 differentially expressed miRNAs (miR-136, 194, 203, 367, 148b, 196b, 26a, 340) (p<0.05). On day 14 post transplant mice in the GVHD cohort developed GVHD as confirmed by organ evaluation (GVHD score: 14–15 out of 20) and weight loss while the control group had no GVHD (GVHD score 0–1 out of 20). The analysis of circulating miRNAs in mice supported the results in humans: the 8 circulating microRNA signature could clearly predict those subjects developing GVHD (area under the ROC curve ≥ 0.75). Of note, pathway enrichment analysis performed using DIANA-mirPath software on the gene targets predicted by microT-4.0, indicate that these miRNAs regulate critical pathways of GVHD pathogenesis (TGFbeta and cytokine signaling, T and B cell differentiation and proliferation, immune response). The analysis of the miRNAs expression profiles of the lymphocytes and of histologically confirmed skin, liver and colon biopsies of GVHD mice highlighted the presence of several deregulated miRNAs when compared to control samples. Pathway enrichment analysis indicated that the differentially expressed miRNAs mainly target genes involved in the TGFbeta and Wnt signaling pathways as well as in the cytoskeleton rearrangements. Of interest, when analysing the expression of the 8 circulating miRNAs able to discriminate GVHD samples from controls, in the organs of mice developing GVHD, miR-203 is also abundant in the skin and colon, miR-367 in the colon and miR-136 in the lymphocytes. These findings strengthen a role for these miRNAs in the modulation of aGVHD and suggest that the presence of plasma miRNAs is linked to the specific organs target of this pathological process. Conclusions: Considering the noninvasive characteristics of plasma sampling and the reproducible and easy detection of miRNAs, our results indicate that circulating miRNAs might represent a promising tool for the early diagnosis of aGVHD thus enhancing therapeutic success and increasing life expectancy of allografted patients. In addition the miRNA profiling of the target organs and lymphocytes of GVHD mice, allowed the identification of several deregulated genes that might play a role in the modulation of aGVHD and warrant further investigations. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4411-4411
Author(s):  
Wei Xiong ◽  
Xiaomei Chen ◽  
Fang Liu ◽  
Xiangjun Chen ◽  
Cong Lu ◽  
...  

Abstract Abstract 4411 MicroRNAs (miRNAs) are small non-coding RNA sequences of about 22nt and play an important role in disease progression including carcinogenesis. Recent evidences reveal that genetic exchange of miRNAs between cells can be accomplished through microvesicles(MVs). MVs are small exosomes of endocytic origin released not only by activated platelets but also by hematologic malignancies such as leukemia. Sheded from the plasma membrane MVs move into the extracellular environment to facilitate communication between cells. MVs containing miRNAs would enable intercellular cross-talk in vivo. This prompted us to investigate specific variations of miRNA expression patterns in MVs derived from leukemia. We examined the miRNA expression profile of MVs both from chronic myeloid leukemia cell line K562 and normal human volunteers’ peripheral blood. Agilent miRNA microarray was employed for detection and then real-time PCR for verification. Bioinformatic software tools were used to predict the target genes of identified microRNAs and define their function. Our study figures out miRNAs of MVs from leukemia and normal cells and characterizes specific miRNAs expression. We found that MVs from K562 cells express 348 miRNAs of 888 miRNAs. While 77 miRNAs displayed down regulation, 134 were upregulated. Interestingly, most of the miRNAs dysregulated in MVs display up regulated expression, suggesting their prevalent roles as tumor promotors. Among the aberrantly expressed miRNAs, miR-1290 was identified whose expression levels was more than 900 times than that of normal cell derived MVs. While the expression of miR-125a-3p was up-regulated by more than 300 times. And miR-654-5p, miR-654-5p, miR-1268 and miR-1246 were up-regulated more than 200 times. Five of the disregulated miRNAs (miR-1290, miR-125a-3p, let-7a, let-7f, miR-26a) were further assayed and validated by Q-RT-PCR results which correlated well with the microarray data. Of note, upexpression of miR-663, miR-1237, miR-149, miR-634, miR-1181, miR-92b, miR-130b as well as downregulation of let-7a, let-7f, miR-26a, miR-26a, miR-26b, miR-266, miR-126, miR-93, miR-451, miR-103, miR-107, miR-27a were similar to what was previously reported about leukemia, thus supporting the general roles of these miRNAs as tumor suppressors or oncomiRNAs in leukemia. Meanwhile we noticed a reduced expression of miR-1237, miR-365, miR-223b, miR-27b, miR-151-5p, miR-23a, miR-21, miR-30e, miR-361-5p, miR-484, miR-185, miR-374a, miR-197 in our study, as recently stated in solid tumor, thus suggesting that significantly lower abundance of these miRNAs is shared in leukemia. In addition to identify the already known leukemia-associated miRNAs, we had checked out dozens of novel miRNAs without any articles published until now, namely miR-502-3p, miR-718, miR-877, miR-1470, miR-720, miR-1267, miR-127, miR-767-3p, miR-1974-v14.0, miR-361-5p, miR-374b and so on. Using bioinformatic tools (TargetScan), we predicted potential targets for those miRNAs that exhibited altered expression in MVs from leukemia cells. Of particular interest, we found that hsa-miR-125a-3p which was refered above may regulate 34 potential genes of which five are located around the chromosome open reading frame. We hypothesised that miR-125a-3p may participate in the modulation of leukemia through these genes by affecting chromosome. Taken together, our study identifies miRNAs of MVs from leukemia and normal cells and characterizes specific miRNAs expression. These findings highlight a number of miRNAs from leukemia-derived MVs that may contribute to the development of hematopoietic malignancies. Further investigation will reveal the function of these differentially expressed miRNAs and may provide potential targets for novel therapeutic strategies. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Joanna Boresowicz ◽  
Paulina Kober ◽  
Natalia Rusetska ◽  
Maria Maksymowicz ◽  
Agnieszka Paziewska ◽  
...  

Purpose. Nonfunctioning gonadotropic pituitary neuroendocrine tumors (PitNETs) are among the most frequent neoplasms of pituitary gland. Although PitNETs are commonly considered benign, a notable part of patients suffer from tumor recurrence after treatment. Invasive growth of pituitary tumor is among the most important prognostic factors. Since molecular features of invasiveness are of potential clinical usefulness, this study was aimed to verify whether invasive and noninvasive nonfunctioning gonadotropic PitNETs differ in the miRNA expression profile and whether the differences could provide a possible molecular classifier. Methods. miRNA profiles were determined in 20 patients (11 invasive and 9 noninvasive tumors) using next-generation sequencing. The expression of selected miRNAs was assessed in the independent cohort of 80 patients with qRT-PCR. Results. When miRNA profiles of invasive and noninvasive tumors were compared, 29 miRNAs were found differentially expressed. Hsa-miR-184, hsa-miR-181a-2-3p, hsa-miR-93-3p, hsa-miR-574-5p, hsa-miR-185-5p, and hsa-miR-3200-5p showed a potential clinical value according to ROC curve analysis. Unfortunately, differential expression of only hsa-miR-185-5p was confirmed in the validation cohort, with AUG at 0.654. Conclusion. Differences in miRNAs expression profiles in invasive and noninvasive gonadotropic PitNETs are slight and the level of miRNA expression seems not to be applicable as useful classifier of tumor invasiveness.


Author(s):  
Sánchez Paula Morales ◽  
Rodero Sandra Rodríguez ◽  
Lourdes Sanz ◽  
Estrella Turienzo ◽  
Rodicio Miravalles José Luis ◽  
...  

Author(s):  
Behnam Emaogolizadeh-Gurd Tapeh ◽  
Mohammad R. Alivand ◽  
Saeed Solalii

: Hypoxia pathway and aberrant miRNA expression profile play crucial roles in the development of various cancers. Recent studies have emphasized that there are many collaborations in this cases because both of them are involved in cancer cell processes, including differentiation, metastasis, and cell proliferation and signaling pathways. Further studies have elucidated that miRNAs affect the hypoxia route, and more interestingly, the hypoxia pathway also affects miRNAs expression profile. The literature review summarizes the fundamental roles of hypoxia-related miRNAs in different cancers. The mutual interactions between miRNAs and hypoxia are a new layer of complexity in cancer hypoxia, which might be helpful in controlling cancer progression. It is also possible that the hypoxia pathway is initiated by miRNAs. In contrast, the hypoxia pathway regulates the expression of a large group of miRNAs. In this review for the first time, we discussed the significant interactions between hypoxia and miRNAs in order to determine new perspectives for new therapeutic aims in the field of cancer.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yan Huang ◽  
Zhe Ma ◽  
Yun-hua Cui ◽  
Hong-sheng Dong ◽  
Ji-meng Zhao ◽  
...  

Objective.This study explored the mechanism of herb-partitioned moxibustion (HM) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) from the miRNA perspective.Methods.Rats were randomly divided into 3 groups [normal control (NC) group, UC model (UC) group, and herb-partitioned moxibustion (UCHM) group]. The UC and UCHM groups were administered 4% DSS for 7 days. The UCHM group received HM at the Tianshu (bilateral, ST25). The effect of HM on UC was observed and the miRNA expression profile in the colon tissues was analyzed.Results.Compared with the UC group, the body weights were significantly higher in the UCHM group on day 14 (P<0.001); the macroscopic colon injury scores and microscopic histopathology scores in the UCHM group decreased (P<0.05); and there were 15 differentially expressed miRNAs in the UCHM group. The changes in miR-184 and miR-490-5p expression levels on the UC were reversed by HM intervention. Validation using qRT-PCR showed that two miRNAs expression trend was consistent with the sequencing results.Conclusion.HM at ST25 might regulate miR-184 and miR-490-5p expression, act on the transcription of their target genes to regulate inflammatory signaling pathways, and attenuate inflammation and tissue injury in the colons of rats with DSS-induced UC.


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