scholarly journals The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Qianyun Feng ◽  
Sheng Zheng ◽  
Jia Zheng

Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20–22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis.

2019 ◽  
Author(s):  
Yunpeng Yang ◽  
Nannan Lang ◽  
Huan Zhang ◽  
Lu Zhang ◽  
Changsheng Chai ◽  
...  

ABSTRACTSmall noncoding RNAs (sncRNAs) are crucial regulatory molecules in organisms and are well known not only for their roles in the control of diverse essential biological processes but also for their value in genetic modification. However, to date, in gram-positive anaerobic solventogenic clostridia (which are a group of important industrial bacteria with exceptional substrate and product diversity), sncRNAs remain minimally explored, leading to a lack of detailed understanding regarding these important molecules and their use as targets for genetic improvement. Here, we performed large-scale phenotypic screens of a transposon-mediated mutant library ofClostridium acetobutylicum, a typical solventogenic clostridial species, and discovered a novel sncRNA (sr8384) that functions as a determinant positive regulator of growth and solvent synthesis. Comparative transcriptomic data combined with genetic and biochemical analyses revealed that sr8384 acts as a pleiotropic regulator and controls multiple targets that are associated with crucial biological processes, through direct or indirect interactions. Notably, modulation of the expression level of either sr8384 or its core target genes significantly increased the growth rate, solvent titer and productivity of the cells, indicating the importance of sr8384-mediated regulatory network inC. acetobutylicum. Furthermore, a homolog of sr8384 was discovered and proven to be functional in another importantClostridiumspecies,C. beijerinckii, suggesting the potential broad role of this sncRNA in clostridia. Our work showcases a previously unknown potent and complex role of sncRNAs in clostridia, providing new opportunities for understanding and engineering these anaerobes, including pathogenicClostridiumspecies.IMPORTANCEThe discovery of sncRNAs as new resources for functional studies and strain modifications are promising strategies in microorganisms. However, these crucial regulatory molecules have hardly been explored in industrially important solventogenic clostridia. Here, we identified sr8384 as a novel determinant sncRNA controlling cellular performance of solventogenicClostridium acetobutylicumand performed detailed functional analysis, which is the most in-depth study of sncRNAs in clostridia to date. We reveal the pleiotropic function of sr8384 and its multiple direct and indirect crucial targets, which represents a valuable source for understanding and optimizing this anaerobe. Of note, manipulation of these targets leads to improved cell growth and solvent synthesis. Our findings provide a new perspective for future studies on regulatory sncRNAs in clostridia.


2021 ◽  
Vol 22 (21) ◽  
pp. 11416
Author(s):  
Maite Caus ◽  
Àuria Eritja ◽  
Milica Bozic

Obesity is a major global health problem and is associated with a significant risk of renal function decline. Obesity-related nephropathy, as one of the complications of obesity, is characterized by a structural and functional damage of the kidney and represents one of the important contributors to the morbidity and mortality worldwide. Despite increasing data linking hyperlipidemia and lipotoxicity to kidney injury, the apprehension of molecular mechanisms leading to a development of kidney damage is scarce. MicroRNAs (miRNAs) are endogenously produced small noncoding RNA molecules with an important function in post-transcriptional regulation of gene expression. miRNAs have been demonstrated to be important regulators of a vast array of physiological and pathological processes in many organs, kidney being one of them. In this review, we present an overview of miRNAs, focusing on their functional role in the pathogenesis of obesity-associated renal pathologies. We explain novel findings regarding miRNA-mediated signaling in obesity-related nephropathies and highlight advantages and future perspectives of the therapeutic application of miRNAs in renal diseases.


Author(s):  
Ashutosh Singh ◽  
Ashutosh Kumar Singh ◽  
Rajanish Giri ◽  
Dhruv Kumar ◽  
Rohit Sharma ◽  
...  

MicroRNAs (miRNAs), a class of small noncoding RNA, posttranscriptionally regulate the expression of genes. Aberrant expression of miRNA is reported in various types of cancer. Since the first report of oncomiR-21 involvement in the glioma, its upregulation was reported in multiple cancers and was allied with high oncogenic property. In addition to the downregulation of tumor suppressor genes, the miR-21 is also associated with cancer resistance to various chemotherapy. The recent research is appraising miR-21 as a promising cancer target and biomarker for early cancer detection. In this review, we briefly explain the biogenesis and regulation of miR-21 in cancer cells. Additionally, the review features the assorted genes/pathways regulated by the miR-21 in various cancer and cancer stem cells.


Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769168 ◽  
Author(s):  
Siying Zhou ◽  
Sijie Zhang ◽  
Hongyu Shen ◽  
Wei Chen ◽  
Hanzi Xu ◽  
...  

Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.


Author(s):  
Le Zhang ◽  
Cuixia Li ◽  
Xiulan Su

AbstractAn increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in diverse cellular processes, including proliferation, apoptosis, migration, invasion, chromatin remodeling, metabolism and immune escape. Clinically, the expression of MIR22HG is increased in many human tumors (colorectal cancer, gastric cancer, hepatocellular carcinoma, lung cancer, and thyroid carcinoma), while in others (esophageal adenocarcinoma and glioblastoma), it is significantly decreased. Moreover, MIR22HG has been reported to function as a competitive endogenous RNA (ceRNA), be involved in signaling pathways, interact with proteins and interplay with miRNAs as a host gene to participate in tumorigenesis and tumor progression. In this review, we describe the biological functions of MIR22HG, reveal its underlying mechanisms for cancer regulation, and highlight the potential role of MIR22HG as a novel cancer prognostic biomarker and therapeutic target that can increase the efficacy of immunotherapy and targeted therapy for cancer treatment.


2019 ◽  
Vol 101 (6) ◽  
pp. 1167-1178 ◽  
Author(s):  
Sarah Bjorkman ◽  
Hugh S Taylor

AbstractMicroRNAs (miRNAs), a class of small noncoding RNA molecules, have been recognized as key post-transcriptional regulators associated with a multitude of human diseases. Global expression profiling studies have uncovered hundreds of miRNAs that are dysregulated in several diseases, and yielded many candidate biomarkers. This review will focus on miRNAs in endometriosis, a common chronic disease affecting nearly 10% of reproductive-aged women, which can cause pelvic pain, infertility, and a myriad of other symptoms. Endometriosis has delayed time to diagnosis when compared to other chronic diseases, as there is no current accurate, easily accessible, and noninvasive tool for diagnosis. Specific miRNAs have been identified as potential biomarkers for this disease in multiple studies. These and other miRNAs have been linked to target genes and functional pathways in disease-specific pathophysiology. Highlighting investigations into the roles of tissue and circulating miRNAs in endometriosis, published through June 2018, this review summarizes new connections between miRNA expression and the pathophysiology of endometriosis, including impacts on fertility. Future applications of miRNA biomarkers for precision medicine in diagnosing and managing endometriosis treatment are also discussed.


2020 ◽  
Vol 19 ◽  
pp. 153303382096746
Author(s):  
Da Liu ◽  
Min Qiu ◽  
Lili Jiang ◽  
Kuiran Liu

The functions of Long noncoding RNA (lncRNA) HOXB-AS1 have been investigated in glioblastoma and multiple myeloma. However, the role of lncRNA HOXB-AS1 in endometrial carcinoma (EC) remains largely unknown. This study investigated the underlying mechanisms of the lncRNA HOXB-AS1 on the progression of EC. In this study, We found that HOXB-AS1 expression was significantly upregulated in EC tissue samples and was associated with shorter survival time. Furthermore, upregulation of HOXB-AS1 promoted proliferation, invasion, and migration of EC cell. HOXB-AS1 and Wnt10b directly bound to miR-149-3p. HOXB-AS1 increased the expression of Wnt10b by binding to miR-149-3p. We further verified the upregulation of β-catenin, cyclin D1, and c-myc induced by HOXB-AS1. In conclusion, our results indicated that HOXB-AS1 exerted oncogenic function as competing endogenous RNA (ceRNA) of miR-149-3p to release Wnt10b and activated Wnt/β-catenin pathway.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jian Wang ◽  
Yong Du ◽  
Xiaoming Liu ◽  
William C. Cho ◽  
Yinxue Yang

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.


2020 ◽  
Vol 27 (2) ◽  
pp. 66-71
Author(s):  
Ozal Arzuman Beylerli ◽  
Ilgiz F. Gareev ◽  
Valentin N. Pavlov

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression at posttranscriptional levels. MiRNAs regulate many normal physiological processes, and also play an important role in the development of most disorders. The expression levels of miRNAs are characterized by endogenous properties and tissue specificity. These characteristics increase the likelihood that miRNAs can serve as useful clinical biomarkers in the diagnosis of certain diseases. Chronic lower back pain is usually associated with degeneration of the intervertebral disc (IDD), which is closely associated with apoptosis, impaired extracellular matrix, cell proliferation, and an inflammatory response. This process is characterized by a cascade of molecular, cellular, biochemical, and structural changes. Currently, there is no clinical therapy that shows the pathophysiology of disk degeneration. The presence of unregulated expression of miRNA in patients with degenerative disk disease indicates a vital role of miRNAs in the pathogenesis of IDD. It becomes apparent that epigenetic processes affect the evolution of IDD as much as the genetic background. Deregulated phenotypes of pulp nucleus cells, including differentiation, migration, proliferation, and apoptosis, are involved in all stages of the progression of human IDD. In this review, we will focus on the role and therapeutic value of miRNAs in IDD.


Author(s):  
Shujun Liu ◽  
Guigang Yan ◽  
Junfu Zhang ◽  
Lianzhi Yu

Evidence suggests that the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in cancer tissues, and its elevated expression is associated with hyperproliferation. However, the underlying mechanisms regarding the role of MALAT1 in retinoblastoma (RB) remain unclear. This study aimed to explore the functional role of MALAT1 in RB by targeting miR-124. The results showed that the expression of MALAT1 was significantly higher in the Y79 cell line than in the ARPE-19 cell line (p < 0.01). Moreover, MALAT1 silence inhibited cell viability, migration, and invasion and promoted apoptosis in Y79 cells (p < 0.05, p < 0.01, or p < 0.001). miR-124 was upregulated by MALAT1 silence and hence was identified as a target of MALAT1 (p < 0.05 or p < 0.001). In addition, miR-124 suppression inhibited cell apoptosis and remarkably abolished the inhibitory effects of MALAT1 silence on cell viability, migration, and invasion (p < 0.05, p < 0.01, or p < 0.001). In addition, Slug was a target of miR-124 and regulated cell viability, migration, invasion, and apoptosis in Y79 cells (p < 0.05, p < 0.01, or p < 0.001). Further, Slug silence abolished miR-124 suppression-induced inactivation of the ERK/MAPK and Wnt/β-catenin pathways. Taken together, our data highlight the pivotal role of MALAT1 in RB. Moreover, the present study elucidated the MALAT1‐miR-124‐ERK/MAPK and Wnt/β-catenin signaling pathways in RB, which might provide a new approach for the treatment of RB.


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