The Emerging Role of Non-Coding RNAs in Osteoarthritis

Osteoarthritis (OS) is the most frequent degenerative condition in the joints, disabling many adults. Several abnormalities in the articular cartilage, subchondral bone, synovial tissue, and meniscus have been detected in the course of OA. Destruction of articular cartilage, the formation of osteophytes, subchondral sclerosis, and hyperplasia of synovial tissue are hallmarks of OA. More recently, several investigations have underscored the regulatory roles of non-coding RNAs (ncRNAs) in OA development. Different classes of non-coding RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), have been reported to affect the development of OA. The expression level of these transcripts has also been used as diagnostic tools in OA. In the present article, we aimed at reporting the role of these transcripts in this process. We need to give a specific angle on the pathology to provide meaningful thoughts on it.

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Subchondral bone remodelling in osteoarthritis

EFORT Open Reviews ◽

10.1302/2058-5241.4.180102 ◽

2019 ◽

Vol 4 (6) ◽

pp. 221-229 ◽

Cited By ~ 8

Author(s):

Simon Donell

Keyword(s):

Bone Marrow ◽

Articular Cartilage ◽

Synovial Fluid ◽

Subchondral Bone ◽

Bone Cells ◽

Bone Remodelling ◽

Delayed Union ◽

Osteophyte Formation ◽

Subchondral Sclerosis

Subchondral bone remodelling is an integral part of osteoarthritis and involves the development of subchondral sclerosis seen on plain imaging, along with osteophyte formation. The development of these changes is due to persistent abnormal mechanical stresses which create a cellular and biomolecular response to microfractures in the subchondral bone and osteochondral junction. An early sign is bone marrow lesions seen on MRI scanning. Healing can occur at this stage by correcting the abnormal loads. Persistence leads to what is thought to be a delayed union or nonunion response by the bone. Microfractures of the osteochondral junction, coupled with articular cartilage fissuring and loss, allows synovial fluid to penetrate the subchondral bone along with cytokines and other molecules reacting with the bone cells to increase the pathological effects. This review gives an overview of the current thoughts on subchondral bone remodelling in osteoarthritis that is aimed at orthopaedic surgeons to help in the understanding of the pathogenesis of osteoarthritis and the role of surgical management. Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180102

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Essential Role of Non-Coding RNAs in Enterovirus Infection: From Basic Mechanisms to Clinical Prospects

International Journal of Molecular Sciences ◽

10.3390/ijms22062904 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2904

Author(s):

Peiyu Zhu ◽

Shuaiyin Chen ◽

Weiguo Zhang ◽

Guangcai Duan ◽

Yuefei Jin

Keyword(s):

Acute Flaccid Paralysis ◽

Foot And Mouth Disease ◽

Human Diseases ◽

Circular Rnas ◽

Enterovirus Infection ◽

Research Directions ◽

Cardiorespiratory Failure ◽

New Ideas ◽

Non Coding Rnas

Enteroviruses (EVs) are common RNA viruses that can cause various types of human diseases and conditions such as hand, foot, and mouth disease (HFMD), myocarditis, meningitis, sepsis, and respiratory disorders. Although EV infections in most patients are generally mild and self-limiting, a small number of young children can develop serious complications such as encephalitis, acute flaccid paralysis, myocarditis, and cardiorespiratory failure, resulting in fatalities. Established evidence has suggested that certain non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) are involved in the occurrence and progression of many human diseases. Recently, the involvement of ncRNAs in the course of EV infection has been reported. Herein, the authors focus on recent advances in the understanding of ncRNAs in EV infection from basic viral pathogenesis to clinical prospects, providing a reference basis and new ideas for disease prevention and research directions.

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CircRNAs and their regulatory roles in cancers

Molecular Medicine ◽

10.1186/s10020-021-00359-3 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Mei Tao ◽

Ming Zheng ◽

Yanhua Xu ◽

Shuo Ma ◽

Weiwei Zhang ◽

...

Keyword(s):

Nuclear Export ◽

Mrna Translation ◽

High Sensitivity ◽

Detection Methods ◽

Circular Rnas ◽

Rnase L ◽

Circular Structure ◽

Dynamic Modification ◽

Non Coding Rnas

AbstractCircular RNAs (circRNAs), a novel type of non-coding RNAs (ncRNAs), have a covalently closed circular structure resulting from pre-mRNA back splicing via spliceosome and ribozymes. They can be classified differently in accordance with different criteria. As circRNAs are abundant, conserved, and stable, they can be used as diagnostic markers in various diseases and targets to develop new therapies. There are various functions of circRNAs, including sponge for miR/proteins, role of scaffolds, templates for translation, and regulators of mRNA translation and stability. Without m7G cap and poly-A tail, circRNAs can still be degraded in several ways, including RNase L, Ago-dependent, and Ago-independent degradation. Increasing evidence indicates that circRNAs can be modified by N-6 methylation (m6A) in many aspects such as biogenesis, nuclear export, translation, and degradation. In addition, they have been proved to play a regulatory role in the progression of various cancers. Recently, methods of detecting circRNAs with high sensitivity and specificity have also been reported. This review presents a detailed overview of circRNAs regarding biogenesis, biomarker, functions, degradation, and dynamic modification as well as their regulatory roles in various cancers. It’s particularly summarized in detail in the biogenesis of circRNAs, regulation of circRNAs by m6A modification and mechanisms by which circRNAs affect tumor progression respectively. Moreover, existing circRNA detection methods and their characteristics are also mentioned.

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Advances in the Identification of Circular RNAs and Research Into circRNAs in Human Diseases

Frontiers in Genetics ◽

10.3389/fgene.2021.665233 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shihu Jiao ◽

Song Wu ◽

Shan Huang ◽

Mingyang Liu ◽

Bo Gao

Keyword(s):

Neurological Disorders ◽

Closed Loop ◽

Significant Proportion ◽

Human Diseases ◽

Circular Rnas ◽

The Status ◽

Research Questions ◽

Non Coding Rnas ◽

Microrna Sponges

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a closed-loop structure that are mainly produced by variable processing of precursor mRNAs (pre-mRNAs). They are widely present in all eukaryotes and are very stable. Currently, circRNA studies have become a hotspot in RNA research. It has been reported that circRNAs constitute a significant proportion of transcript expression, and some are significantly more abundantly expressed than other transcripts. CircRNAs have regulatory roles in gene expression and critical biological functions in the development of organisms, such as acting as microRNA sponges or as endogenous RNAs and biomarkers. As such, they may have useful functions in the diagnosis and treatment of diseases. CircRNAs have been found to play an important role in the development of several diseases, including atherosclerosis, neurological disorders, diabetes, and cancer. In this paper, we review the status of circRNA research, describe circRNA-related databases and the identification of circRNAs, discuss the role of circRNAs in human diseases such as colon cancer, atherosclerosis, and gastric cancer, and identify remaining research questions related to circRNAs.

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Discovery of pluripotency-associated microRNAs in rabbit preimplantation embryos and embryonic stem-like cells

Reproduction ◽

10.1530/rep-12-0259 ◽

2013 ◽

Vol 145 (4) ◽

pp. 421-437 ◽

Cited By ~ 12

Author(s):

Pouneh Maraghechi ◽

László Hiripi ◽

Gábor Tóth ◽

Babett Bontovics ◽

Zsuzsanna Bősze ◽

...

Keyword(s):

Embryonic Development ◽

Cell Biology ◽

Embryonic Stem ◽

Blastocyst Stage ◽

Expression Level ◽

Preimplantation Embryos ◽

Regulatory Function ◽

Low Level ◽

Non Coding Rnas

MicroRNAs (miRNAs) are small non-coding RNAs that regulate multiple biological processes. Increasing experimental evidence implies an important regulatory role of miRNAs during embryonic development and in embryonic stem (ES) cell biology. In the current study, we have described and analyzed the expression profile of pluripotency-associated miRNAs in rabbit embryos and ES-like cells. The rabbit specific ocu-miR-302 and ocu-miR-290 clusters, and three homologs of the human C19MC cluster (ocu-miR-512, ocu-miR-520e, and ocu-miR-498) were identified in rabbit preimplantation embryos and ES-like cells. The ocu-miR-302 cluster was highly similar to its human homolog, while ocu-miR-290 revealed a low level of evolutionary conservation with its mouse homologous cluster. The expression of the ocu-miR-302 cluster began at the 3.5 days post-coitum early blastocyst stage and they stayed highly expressed in rabbit ES-like cells. In contrast, a high expression level of the ocu-miR-290 cluster was detected during preimplantation embryonic development, but a low level of expression was found in rabbit ES-like cells. Differential expression of the ocu-miR-302 cluster and ocu-miR-512 miRNA was detected in rabbit trophoblast and embryoblast. We also found that Lefty has two potential target sites in its 3′UTR for ocu-miR-302a and its expression level increased upon ocu-miR-302a inhibition. We suggest that the expression of the ocu-miR-302 cluster is characteristic of the rabbit ES-like cell, while the ocu-miR-290 cluster may play a crucial role during early embryonic development. This study presents the first identification, to our knowledge, of pluripotency-associated miRNAs in rabbit preimplantation embryos and ES-like cells, which can open up new avenues to investigate the regulatory function of ocu-miRNAs in embryonic development and stem cell biology.

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Role of circular RNAs in cardiovascular diseases

Experimental Biology and Medicine ◽

10.1177/1535370218822988 ◽

2019 ◽

Vol 244 (2) ◽

pp. 73-82 ◽

Cited By ~ 2

Author(s):

Xue Gong ◽

Gengze Wu ◽

Chunyu Zeng

Keyword(s):

Cardiovascular Diseases ◽

Critical Role ◽

Developed Countries ◽

Circular Rnas ◽

Promising Target ◽

The Central Nervous System ◽

Non Coding Rnas ◽

Expression Abundance ◽

Therapeutic Perspective

Over the last several decades, cardiovascular diseases largely increase the morbidity and mortality especially in developed countries, affecting millions of people worldwide. Although extensive work over the last two decades attempted to decipher the molecular network of regulating the pathogenesis and progression of these diseases, evidences from clinical trials with newly revealed targets failed to show more evidently salutary effects, indicating the inefficiency of understanding the complete regulatory landscape. Recent studies have shifted their focus from coding genes to the non-coding ones, which consist of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and the lately re-discovered a unique group of RNAs—circular RNAs (circRNAs). As the focus now has been shifted to the newly identified group of non-coding RNAs, circRNAs exhibit stability, highly conservation and relative enriched expression abundance in some cases, which are distinct from their cognate linear counterparts—lncRNAs. So far, emerging evidence begins to support the critical role of circRNAs in organogenesis and pathogenesis as exemplified in the central nervous system, and could be just as implicative in the cardiovascular system, suggesting a therapeutic perspective in related diseases. Impact statement Circular RNAs are important regulators of multiple biological processes such as organogenesis and oncogenesis. Although the bulk of concerning studies focused on revealing their diversified roles in various types of cancers, reports began to accumulate in cardiovascular field these days. We summarize circular RNAs implicated in cardiovascular diseases, aiming to highlight the advances in the knowledge of such diseases and their potential of being promising target for diagnosis and therapy.

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The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.696705 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xinyao Hu ◽

Hua Zhu ◽

Yang Shen ◽

Xiaoyu Zhang ◽

Xiaoqin He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Vital Role ◽

Circular Rnas ◽

First Line ◽

Advanced Hcc ◽

Chemotherapy Agent ◽

Development Of Resistance ◽

Non Coding Rnas

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Sorafenib is approved by the U.S. Food and Drug Administration to be a first-line chemotherapy agent for patients with advanced HCC. A portion of advanced HCC patients can benefit from the treatment with sorafenib, but many patients ultimately develop sorafenib resistance, leading to a poor prognosis. The molecular mechanisms of sorafenib resistance are sophisticated and indefinite. Notably, non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are critically participated in the occurrence and progression of tumors. Moreover, growing evidence has suggested that ncRNAs are crucial regulators in the development of resistance to sorafenib. Herein, we integrally and systematically summarized the molecular mechanisms and vital role of ncRNAs impact sorafenib resistance of HCC, and ultimately explored the potential clinical administrations of ncRNAs as new prognostic biomarkers and therapeutic targets for HCC.

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The Emerging Role of Non-Coding RNAs in Pituitary Gland Tumors and Meningioma

Cancers ◽

10.3390/cancers13235987 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5987

Author(s):

Soudeh Ghafouri-Fard ◽

Atefe Abak ◽

Bashdar Mahmud Hussen ◽

Mohammad Taheri ◽

Guive Sharifi

Keyword(s):

Brain Tumors ◽

Pituitary Gland ◽

Pituitary Tumors ◽

Circular Rnas ◽

Current Review ◽

Non Coding Rnas

Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are non-coding transcripts which are involved in the pathogenesis of pituitary gland tumors. LncRNAs that participate in the pathogenesis of pituitary gland tumors mainly serve as sponges for miRNAs. CLRN1-AS1/miR-217, XIST/miR-424-5p, H19/miR-93a, LINC00473/miR-502-3p, SNHG7/miR-449a, MEG8/miR-454-3p, MEG3/miR-23b-3p, MEG3/miR-376B-3P, SNHG6/miR-944, PCAT6/miR-139-3p, lncRNA-m433s1/miR-433, TUG1/miR-187-3p, SNHG1/miR-187-3p, SNHG1/miR-302, SNHG1/miR-372, SNHG1/miR-373, and SNHG1/miR-520 are identified lncRNA/miRNA pairs that are involved in this process. Hsa_circ_0001368 and circOMA1 are two examples of circRNAs that contribute to the pathogenesis of pituitary gland tumors. Meanwhile, SNHG1, LINC00702, LINC00460, and MEG3 have been found to partake in the pathogenesis of meningioma. In the current review, we describe the role of non-coding RNAs in two types of brain tumors, i.e., pituitary tumors and meningioma.

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Sophisticated Gene Regulation for a Complex Physiological System: The Role of Non-coding RNAs in Photoreceptor Cells

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.629158 ◽

2021 ◽

Vol 8 ◽

Author(s):

Sabrina Carrella ◽

Sandro Banfi ◽

Marianthi Karali

Keyword(s):

Molecular Mechanisms ◽

Developmental Process ◽

Photoreceptor Cells ◽

Sensory Transduction ◽

Circular Rnas ◽

Therapeutic Implications ◽

Physiological Processes ◽

Non Coding Rnas ◽

And Function

Photoreceptors (PRs) are specialized neuroepithelial cells of the retina responsible for sensory transduction of light stimuli. In the highly structured vertebrate retina, PRs have a highly polarized modular structure to accommodate the demanding processes of phototransduction and the visual cycle. Because of their function, PRs are exposed to continuous cellular stress. PRs are therefore under pressure to maintain their function in defiance of constant environmental perturbation, besides being part of a highly sophisticated developmental process. All this translates into the need for tightly regulated and responsive molecular mechanisms that can reinforce transcriptional programs. It is commonly accepted that regulatory non-coding RNAs (ncRNAs), and in particular microRNAs (miRNAs), are not only involved but indeed central in conferring robustness and accuracy to developmental and physiological processes. Here we integrate recent findings on the role of regulatory ncRNAs (e.g., miRNAs, lncRNAs, circular RNAs, and antisense RNAs), and of their contribution to PR pathophysiology. We also outline the therapeutic implications of translational studies that harness ncRNAs to prevent PR degeneration and promote their survival and function.

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Non-Coding RNAs: Uncharted Mediators of Thyroid Cancer Pathogenesis

Cancers ◽

10.3390/cancers12113264 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3264

Author(s):

Hossein Tabatabaeian ◽

Samantha Peiling Yang ◽

Yvonne Tay

Keyword(s):

Thyroid Cancer ◽

Cancer Patients ◽

Molecular Mechanisms ◽

Endocrine System ◽

Circular Rnas ◽

Poor Overall Survival ◽

Cancer Pathogenesis ◽

Critical Issues ◽

Non Coding Rnas

Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the poor overall survival of undifferentiated and metastatic thyroid cancer patients. Recent studies have revealed the role of different non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are dysregulated during thyroid cancer development or the acquisition of resistance to therapeutics, and may play key roles in treatment failure and poor prognosis of the thyroid cancer patients. Here, we systematically review the emerging roles and molecular mechanisms of ncRNAs that regulate thyroid tumorigenesis and drug response. We then propose the potential clinical implications of ncRNAs as novel diagnostic and prognostic biomarkers for thyroid cancer.

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