scholarly journals The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mengge Sun ◽  
Xiaoya Zhou ◽  
Lili Chen ◽  
Shishu Huang ◽  
Victor Leung ◽  
...  

MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

Author(s):  
Yan-man Zhou ◽  
Yu-ying Yang ◽  
Yi-xuan Jing ◽  
Tian-jiao Yuan ◽  
Li-hao Sun ◽  
...  

2021 ◽  
Vol 11 (8) ◽  
pp. 3654
Author(s):  
Brigitte Sipos ◽  
Peter Jirak ◽  
Vera Paar ◽  
Richard Rezar ◽  
Moritz Mirna ◽  
...  

Cardiovascular diseases remain the most common causes of death globally, according to the World Health Organization. In recent years, a great number of biomarkers have been investigated, whereas only some have gained value in the diagnosis, prognosis, and risk stratification of different cardiovascular illnesses. As numerous studies have investigated the diagnostic yield of novel biomarkers in various disease entities every year, this review aims to provide an overview of the current status of four promising representatives. In particular, this manuscript refers to soluble suppression of tumorigenicity 2 (sST2), heart-type fatty acid binding protein (H-FABP), growth differentiation factor (GDF-15) and soluble urokinase-type plasminogen activator receptor (suPAR). These markers are of special interest as they are thought to provide an accurate estimate of cardiovascular risk in certain patient populations, especially those with pre-existing diseases, such as obesity or diabetes mellitus. We sought to give an overview of their function, individual diagnostic and predictive value and determination in the laboratory. A review of the literature regarding the aforementioned cardiovascular biomarkers yielded manifold results with respect to their individual diagnostic and prognostic value. Yet, the clinical relevance of these findings remains unclear, warranting further studies to identify their optimal use in clinical routine.


2021 ◽  
Vol 20 ◽  
pp. 153303382199208 ◽  
Author(s):  
Meng Wu ◽  
Qingdai Li ◽  
Hongbing Wang

Background: Breast cancer is the most commonly diagnosed malignancy and a major cause of cancer-related deaths in women globally. Identification of novel prognostic and pathogenesis biomarkers play a pivotal role in the management of the disease. Methods: Three data sets from the GEO database were used to identify differentially expressed genes (DEGs) in breast cancer. Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway analyses were performed to elucidate the functional roles of the DEGs. Besides, we investigated the translational and protein expression levels and survival data of the DEGs in patients with breast cancer from the Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, Human Protein Atlas, and Kaplan Meier plotter tool databases. The corresponding change in the expression level of microRNAs in the DEGs was also predicted using miRWalk and TargetScan, and the expression profiles were analyzed using OncomiR. Finally, the expression of novel DEGs were validated in Chinese breast cancer tissues by RT-qPCR. Results: A total of 46 DEGs were identified, and GO analysis revealed that these genes were mainly associated with biological processes involved in fatty acid, lipid localization, and regulation of lipid metabolism. Two novel biomarkers, ADH1A and IGSF10, and 4 other genes ( APOD, KIT, RBP4, and SFRP1) that were implicated in the prognosis and pathogenesis of breast cancer, exhibited low expression levels in breast cancer tissues. Besides, 14/25 microRNAs targeting 6 genes were first predicted to be associated with breast cancer prognosis. RT-qPCR results of ADH1A and IGSF10 expression in Chinese breast cancer tissues were consistent with the database analysis and showed significant down-regulation. Conclusion: ADH1A, IGSF10, and the 14 microRNAs were found to be potential novel biomarkers for the diagnosis, treatment, and prognosis of breast cancer.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Zhang Xin ◽  
Liu L Ping

Background and Objective: MicroRNAs have been shown to regulate in several pathological process of intracranial aneurysms. The study aimed to estimate whether miRNAs have the potential to become novel biomarkers for intracranial aneurysm rupture. Materials and methods Forty-five ruptured intracranial aneurysm patients were enrolled according to the inclusion criteria, meanwhile thirty-five healthy individuals were recruited in this study. Differentially expressed plasma miRNA profiles were screened in five pairs of patients and controls in microarray study. Then validation was performed in the rest of the objects using quantitative real-time PCR assays. Results: Fourteen significantly changed miRNAs were screened out from patients with aneurysms compared with healthy controls. More than three thousand target genes related to these disregulated miRNAs were found and bioinformatic analysis revealed that these miRNA were involved in intracranial aneurysm development and rupture. Ultimately four miRNAs from screening profile and one supplementary miRNA were demonstrated to be significantly altered. Conclusion: We demonstrated that several miRNAs were differentially expressed among ruptured aneurysm patients and healthy participants, and plasma miRNAs may be novel diagnostic biomarkers in intracranial aneurysm rupture.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mi-Soon Han ◽  
Jae Myun Lee ◽  
Soo-Nyung Kim ◽  
Jae-Hoon Kim ◽  
Hyon-Suk Kim

Almost all cervical cancers are associated with human papillomavirus (HPV); however, the majority of women infected with this virus do not develop cervical cancer. Therefore, new markers are needed for reliable screening of cervical cancer, especially in relation to HPV infection. We aimed to identify potential microRNAs that may serve as diagnostic markers for cervical cancer development in high-risk HPV-positive patients. We evaluated the microRNA expression profiles in 12 cervical tissues using the hybridization method and verified them by quantitative polymerase chain reaction (qPCR). Finally, we evaluated the effects of HPV16 oncoproteins on the expression of selected microRNAs using cervical cancer cells (CaSki and SiHa) and RNA interference. With the hybridization method, eight microRNAs (miR-9-5p, miR-136-5p, miR-148a-3p, miR-190a-5p, miR-199b-5p, miR-382-5p, miR-597-5p, and miR-655-3p) were found to be expressed differently in the HPV16-positive cervical cancer group and HPV16-positive normal group (fold change ≥ 2). The results of qPCR showed that miR-148a-3p, miR-190a-5p, miR-199b-5p, and miR-655-3p levels significantly decreased in the cancer group compared with the normal group. Upon silencing of HPV16 E5 and E6/E7, miR-148a-3p levels increased in both cell lines. Silencing of E6/E7 in SiHa cells led to the increase in miR-199b-5p and miR-190a-5p levels. Three HPV16 oncoproteins (E5, E6, and E7) downregulate miR-148a-3p, while E6/E7 inhibit miR-199b-5p and miR-190a-5p expression in cervical carcinoma. The three microRNAs, miR-148a-3p, miR-199b-5p, and miR-190a-5p, may be novel diagnostic biomarkers for cervical cancer development in high-risk HPV-positive patients.


2017 ◽  
Vol 195 ◽  
pp. 137-142 ◽  
Author(s):  
Mi Hye Kim ◽  
Hye Ji Lee ◽  
Jung-Chul Park ◽  
Jongki Hong ◽  
Woong Mo Yang

2005 ◽  
Vol 288 (6) ◽  
pp. C1211-C1221 ◽  
Author(s):  
Steven J. Pardo ◽  
Mamta J. Patel ◽  
Michelle C. Sykes ◽  
Manu O. Platt ◽  
Nolan L. Boyd ◽  
...  

Exposure to microgravity causes bone loss in humans, and the underlying mechanism is thought to be at least partially due to a decrease in bone formation by osteoblasts. In the present study, we examined the hypothesis that microgravity changes osteoblast gene expression profiles, resulting in bone loss. For this study, we developed an in vitro system that simulates microgravity using the Random Positioning Machine (RPM) to study the effects of microgravity on 2T3 preosteoblast cells grown in gas-permeable culture disks. Exposure of 2T3 cells to simulated microgravity using the RPM for up to 9 days significantly inhibited alkaline phosphatase activity, recapitulating a bone loss response that occurs in real microgravity conditions without altering cell proliferation and shape. Next, we performed DNA microarray analysis to determine the gene expression profile of 2T3 cells exposed to 3 days of simulated microgravity. Among 10,000 genes examined using the microarray, 88 were downregulated and 52 were upregulated significantly more than twofold using simulated microgravity compared with the static 1-g condition. We then verified the microarray data for some of the genes relevant in bone biology using real-time PCR assays and immunoblotting. We confirmed that microgravity downregulated levels of alkaline phosphatase, runt-related transcription factor 2, osteomodulin, and parathyroid hormone receptor 1 mRNA; upregulated cathepsin K mRNA; and did not significantly affect bone morphogenic protein 4 and cystatin C protein levels. The identification of gravisensitive genes provides useful insight that may lead to further hypotheses regarding their roles in not only microgravity-induced bone loss but also the general patient population with similar pathological conditions, such as osteoporosis.


2014 ◽  
Vol 3 (1) ◽  
Author(s):  
Claudia Campanella ◽  
Celeste Caruso Bavisotto ◽  
Antonella Marino Gammazza ◽  
Dragana Nikolic ◽  
Francesca Rappa ◽  
...  

Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exosomal Hsps offer significant opportunities for clinical applications, including their use as potential novel biomarkers for the diagnoses or prognoses of different diseases, or for therapeutic applications and drug delivery.


Author(s):  
Ya-Ke Lu ◽  
Xi Chu ◽  
Shuo Wang ◽  
Yue Sun ◽  
Jie Zhang ◽  
...  

Abstract Context Circular RNAs (circRNAs), which are involved in the development of diseases by regulating gene expression, have become promising novel biomarkers for diseases. Objective The aim of the present study was to identify the circulating circRNA biomarkers for early detection of type 2 diabetes (T2D). Methods The circRNA expression profiles were screened by microarray and compared between 5 new T2D cases and 5 healthy controls. The expression of candidate circRNAs that may be involved in the insulin phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway were validated by RT-qPCR in a second sample with 30 T2D cases and 30 controls. The association between circRNAs and T2D and their clinical significances were further assessed by logistic regression model, correlation analysis, and ROC curve in a large cohort comprising 313 subjects. The microRNA (miRNA) targets of circRNAs were verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results Low expressed circ_0063425 and hsa_circ_0056891 were independent predictors of T2D, impaired fasting glucose (IFG), and insulin resistance. The 2-circRNA panel had a high diagnostic accuracy for discriminating T2D and IFG from healthy controls, especially when body mass index was integrated. miR-19a-3p and miR-1-3p were identified as the miRNA targets of hsa_circ_0063425 and hsa_circ_0056891, respectively. Significant positive correlations were found between the expression levels of AKT and hsa_circ_0063425, PI3K and hsa_circ_0056891, in the total sample and subgroups stratified by glucose levels. Conclusion Downregulated hsa_circ_0063425 and hsa_circ_0056891 might contribute to the pathogenesis of T2D. They are valuable circulating biomarkers for early detection of T2D, which may be involved in regulation of PI3K/AKT signaling.


Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76558-76573 ◽  
Author(s):  
Ting Zheng ◽  
Ju-Hee Kang ◽  
Jung-Sun Sim ◽  
Jung-Woo Kim ◽  
Jeong-Tae Koh ◽  
...  

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