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Reduced Circulating Levels of miR-433 and miR-133b Are Potential Biomarkers for Parkinson's Disease.

ABSTRACT: Aberrant expression of microRNA (miRNA) in tissues may lead to altered level in circulation. Considerable evidence has suggested that miRNA deregulation is involved in the pathogenesis of Parkinson's disease (PD). In this study, we screened a set of PD-associated miRNAs and aimed to identify differentially expressed miRNAs in plasma of PD patients and to evaluate their potentiality to serve as PD biomarkers. A total of 95 subjects consisting of 46 sporadic PD cases and 49 controls were recruited. Plasma levels of six miRNAs including miR-433, miR-133b, miR-34b, miR-34c, miR-153, and miR-7 were evaluated using reverse transcribed quantitative PCR, among which we found that miR-34c and miR-7 were below detection limit under our condition. The results showed that levels of circulating miR-433 (P = 0.003) and miR-133b (P = 0.006), but not miR-34b and miR-153, were reduced in PD patients. miR-433 and miR-133b were strongly correlated in both control and PD groups (rs = 0.87 and 0.85, respectively). The correlation between miR-34b and miR-153 expressions was significantly reduced (P < 0.05) in the PD group. Although miR-433 and miR-133b were likely to be functionally complimentary as suggested by Pathway and Gene Ontology analyses, these two miRNAs per se might not be sufficient to predict PD. No correlation was observed between the four miRNAs and age or severity of disease. Collectively, our results demonstrate that circulating miR-433 and miR-133b are significantly altered in PD and may serve as PD biomarkers.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5481393 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Reduced Circulating Levels of miR-433 and miR-133b Are Potential Biomarkers for Parkinson's Disease.

Zhang Xiong X Yang Rui R Hu Bei-Lei BL Lu Pengcheng P Zhou Li-Li LL He Zhi-Yong ZY Wu Hong-Mei HM Zhu Jian-Hong JH

Frontiers in cellular neuroscience 20170623

Aberrant expression of microRNA (miRNA) in tissues may lead to altered level in circulation. Considerable evidence has suggested that miRNA deregulation is involved in the pathogenesis of Parkinson's disease (PD). In this study, we screened a set of PD-associated miRNAs and aimed to identify differentially expressed miRNAs in plasma of PD patients and to evaluate their potentiality to serve as PD biomarkers. A total of 95 subjects consisting of 46 sporadic PD cases and 49 controls were recruited ...[more]

PMID: 28690499

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Project description:BackgroundSmall molecule RNAs (miRNAs) could induce downregulation of α-synuclein (SNCA) expression by binding the 3' untranslated region of SNCA, thus playing an important role in the pathogenesis of Parkinson's disease (PD). Recent studies suggest that SNCA-related miRNAs in saliva are promising PD biomarkers. Research on those miRNAs in plasma is rare in patients with PD.ObjectiveTo detect the plasma expression levels of three SNCA related miRNAs (miR-7, miR-153, and miR-223) in PD, and to explore their diagnostic value and associations with clinical phenotype.MethodsMiR-7, miR-153, and miR-223 levels were detected in the plasma of 75 PD patients and 73 normal controls (NCs) via real-time quantitative polymerase chain reaction. The receiver operating characteristic (ROC) curves were delineated to evaluate their diagnostic value in PD. In addition, their associations with demographic, key motor, and non-motor symptoms were explored by serial scales.ResultsThe expression levels of plasma miR-153 and miR-223 were significantly decreased in patients with PD relative to NCs. The area under the ROC curve separating PD from NCs was 63.1% for miR-153 and 86.2% for miR-223, respectively. The plasma miR-153 level in de novo PD was lower than that in treated patients (p = 0.006), its level increased gradually with disease duration (r = 0.358, p = 0.002) and Unified Parkinson's Disease Rating Scale Part III score (r = 0.264, p = 0.022). Plasma miR-223 level was decreased in patients with clinical possible rapid eye movement sleep behavior disorder (cpRBD) compared with those without cpRBD (p < 0.001), and its level was negatively associated with RBDSQ score (r = -0.334, p = 0.003). Multiple linear regression analysis revealed that disease duration (p = 0.049) was the independently associated factor of miR-153 level; whereas, RBDSQ (p = 0.009) was related to miR-223 level in PD.ConclusionPlasma miR-153 and miR-223 levels could be potential biomarkers of PD.

Project description:Rhabdomyosarcoma (RMS) arises from myogenic precursors that fail to complete muscle differentiation and represents the most frequent soft tissue sarcoma in children. Two major histological subtypes are recognized: alveolar RMS, characterized by a more aggressive behavior and a greater proneness to metastasis, and embryonal RMS which accounts for the 80% of cases and carries a better prognosis. Despite the survival of patients with localized tumors has progressively improved, RMS remains a challenging disease especially for metastatic patients and in case of progressive or recurrent disease after front-line therapy. MicroRNAs, a class of small non-coding RNA, have emerged as crucial players in cancer development and progression, and their detection in plasma (circulating miRNAs) represents a promising minimally invasive approach that deserve to be exploited in clinical practice. We evaluated the utility of circulating miRNAs as diagnostic and prognostic biomarkers in children with RMS profiling miRNAs from plasma of a small cohort of RMS patients and healthy donors (HD) using a qPCR Cancer Panel. An assessment of hemolysis status of plasma using miR-451/miR-23a ratio was performed as pre-analytical analysis. Statistical analysis revealed that miRNAs expression pattern clearly distinguished RMS patients from HD (p < 0.05). Interestingly, plasma levels of muscle-specific miR-206 were found to be significantly increased in RMS patients compared to HD, whereas levels of three potential tumor-suppressor miRNAs, miR-26a and miR-30b/30c, were found lower. Reduced levels of circulating miR-26a and miR-30b/c were further measured in an independent larger cohort of patients (validation set) by digital droplet PCR. In particular, we evidenced that miR-26a absolute plasma levels were associated with fusion status and adverse outcome (p < 0.05). Taken together, these findings demonstrate the potential of circulating miRNA as diagnostic and prognostic biomarker in children affected by this malignancy and enforced the key role of miR-26a in pediatric rhabdomyosarcoma.

Project description:The present study aimed to investigate the expression levels and clinical significance of microRNA (miR)-203 and miR-133b in laryngeal carcinoma. A total of 154 patients with laryngeal carcinoma (research group) along with 100 healthy individuals (control group) were enrolled in the study. The patients were admitted to Yidu Central Hospital of Weifang (Weifang, China) from February 2016 to October 2018. Fasting venous blood (5 ml) was extracted from all subjects to determine the expression levels of serum miR-203 and miR-133b by reverse transcription-quantitative polymerase chain reaction (PCR) and to compare them among patients with different pathological characteristics. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic values of miR-203 and miR-133b for laryngeal carcinoma. The research group showed significantly lower expression levels of miR-203 and miR-133b than the control group (P<0.05). According to ROC curve analysis, when the cut-off value was 0.659, the sensitivity and specificity of miR-203 in diagnosing laryngeal carcinoma were 60.00 and 90.26%, respectively, whereas when the cut-off value was 1.398, the sensitivity and specificity of miR-133b were 55.00 and 87.66%, respectively. The sensitivity and specificity of the joint detection were 70.00 and 83.77%, respectively, when the cut-off value was 0.416. In the research group, miR-203 was expressed significantly different in patients with different pathological stages and tumor types (P<0.050). The expression of miR-133b varied significantly in patients with different pathological stages, differentiation degrees and lymph node metastasis (P<0.050). In conclusion, miR-203 and miR-133b were expressed at low levels in patients with laryngeal carcinoma. The expression of miR-203 was related to tumor-node-metastasis (TNM) stage and tumor type, whereas the expression of miR-133b was related to TNM stage, differentiation degree, as well as lymph node metastasis. Joint detection of miR-203 and miR-133b is expected to be an excellent marker for the diagnosis and treatment of laryngeal carcinoma.

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Reduced Circulating Levels of miR-433 and miR-133b Are Potential Biomarkers for Parkinson's Disease.

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Reduced Circulating Levels of miR-433 and miR-133b Are Potential Biomarkers for Parkinson's Disease.

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