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16 pages, 2344 KiB

Open AccessArticle

Resveratrol Attenuates the Mitochondrial RNA-Mediated Cellular Response to Immunogenic Stress

by Jimin Yoon, Doyeong Ku, Minseok Lee, Namseok Lee, Sung Gap Im and Yoosik Kim

Int. J. Mol. Sci. 2023, 24(8), 7403; https://doi.org/10.3390/ijms24087403 - 17 Apr 2023

Cited by 3 | Viewed by 1956

Human mitochondria contain a circular genome that encodes 13 subunits of the oxidative phosphorylation system. In addition to their role as powerhouses of the cells, mitochondria are also involved in innate immunity as the mitochondrial genome generates long double-stranded RNAs (dsRNAs) that can [...] Read more.

Human mitochondria contain a circular genome that encodes 13 subunits of the oxidative phosphorylation system. In addition to their role as powerhouses of the cells, mitochondria are also involved in innate immunity as the mitochondrial genome generates long double-stranded RNAs (dsRNAs) that can activate the dsRNA-sensing pattern recognition receptors. Recent evidence shows that these mitochondrial dsRNAs (mt-dsRNAs) are closely associated with the pathogenesis of human diseases that accompany inflammation and aberrant immune activation, such as Huntington’s disease, osteoarthritis, and autoimmune Sjögren’s syndrome. Yet, small chemicals that can protect cells from a mt-dsRNA-mediated immune response remain largely unexplored. Here, we investigate the potential of resveratrol (RES), a plant-derived polyphenol with antioxidant properties, on suppressing mt-dsRNA-mediated immune activation. We show that RES can revert the downstream response to immunogenic stressors that elevate mitochondrial RNA expressions, such as stimulation by exogenous dsRNAs or inhibition of ATP synthase. Through high-throughput sequencing, we find that RES can regulate mt-dsRNA expression, interferon response, and other cellular responses induced by these stressors. Notably, RES treatment fails to counter the effect of an endoplasmic reticulum stressor that does not affect the expression of mitochondrial RNAs. Overall, our study demonstrates the potential usage of RES to alleviate the mt-dsRNA-mediated immunogenic stress response. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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23 pages, 5747 KiB

Open AccessArticle

The Human Cytomegalovirus β2.7 Long Non-Coding RNA Prevents Induction of Reactive Oxygen Species to Maintain Viral Gene Silencing during Latency

by Marianne R. Perera and John H. Sinclair

Int. J. Mol. Sci. 2022, 23(19), 11017; https://doi.org/10.3390/ijms231911017 - 20 Sep 2022

Cited by 2 | Viewed by 1767

Abstract

Human cytomegalovirus (HCMV) is a significant source of disease for the immunosuppressed and immunonaive. The treatment of HCMV is made more problematic by viral latency, a lifecycle stage in which the virus reduces its own gene expression and produces no infectious virus. The [...] Read more.

Human cytomegalovirus (HCMV) is a significant source of disease for the immunosuppressed and immunonaive. The treatment of HCMV is made more problematic by viral latency, a lifecycle stage in which the virus reduces its own gene expression and produces no infectious virus. The most highly expressed viral gene during HCMV latency is the viral β2.7 long non-coding RNA. Although we have recently shown that the β2.7 lncRNA lowers levels of reactive oxygen species (ROS) during infection in monocytes, how this impacts latency is unclear. We now show that β2.7 is important for establishing and maintaining HCMV latency by aiding the suppression of viral lytic gene expression and that this is directly related to its ability to quench reactive oxygen species (ROS). Consistent with this, we also find that exogenous inducers of ROS cause reactivation of latent HCMV. These effects can be compensated by treatment with an antioxidant to lower ROS levels. Finally, we show that ROS-mediated reactivation is independent of myeloid differentiation, but instead relies on NF-κB activation. Altogether, these results reveal a novel factor that is central to the complex process that underpins HCMV latency. These findings may be of particular relevance in the transplant setting, in which transplanted tissue/organs are subject to very high ROS levels, and HCMV reactivation poses a significant threat. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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16 pages, 5436 KiB

Open AccessArticle

CircDCLRE1C Regulated Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Regulating miR-214b-3p/STAT3 Pathway in Macrophages

by Yibin Xu, Yulin Huang, Siyu Zhang, Lijin Guo, Ruiquan Wu, Xiang Fang, Xiaolan Chen, Haiping Xu and Qinghua Nie

Int. J. Mol. Sci. 2022, 23(12), 6822; https://doi.org/10.3390/ijms23126822 - 19 Jun 2022

Cited by 1 | Viewed by 1900

Abstract

The immune cell inflammation response is closely related to the occurrence of disease, and much evidence has shown that circular RNAs (circRNAs) play vital roles in the occurrence of disease. However, the biological function and regulatory mechanisms of circRNAs in the immune cell [...] Read more.

The immune cell inflammation response is closely related to the occurrence of disease, and much evidence has shown that circular RNAs (circRNAs) play vital roles in the occurrence of disease. However, the biological function and regulatory mechanisms of circRNAs in the immune cell inflammation response remain poorly understood. In this study, we constructed an inflammatory model using lipopolysaccharide (LPS)-stimulated chicken macrophage lines (also known as HD11) to verify the function and mechanism of the novel circDCLRE1C (ID: gga_circ_0001674), which was significantly upregulated in spleen tissues infected by coccidia and the macrophage cells exposed to LPS. The results showed that circDCLRE1C aggravated LPS-induced inflammation and apoptosis in HD11 cells. Systemically, circDCLRE1C acted as a sponge for miR-214b-3p binding sites thereby regulating the expression of STAT3. The overexpression of miR-214b-3p rescued the pro-inflammatory effect of circDCLRE1C in HD11 cells stimulated with LPS, and rescued the high expression of STAT3. In conclusion, our study showed that circDCLRE1C could aggravate LPS-induced inflammation and apoptosis through competitive adsorption of miR-214b-3p, thereby increasing the expression of STAT3. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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13 pages, 1972 KiB

Open AccessArticle

Enhancer RNA AL928768.3 from the IGH Locus Regulates MYC Expression and Controls the Proliferation and Chemoresistance of Burkitt Lymphoma Cells with IGH/MYC Translocation

by Ekaterina Mikhailovna Stasevich, Aksinya Nicolaevna Uvarova, Matvey Mikhailovich Murashko, Elmira Ramilevna Khabusheva, Saveliy Andreevich Sheetikov, Vladimir Sergeyevich Prassolov, Dmitriy Vladimirovich Kuprash, Denis Eriksonovich Demin and Anton Markovich Schwartz

Int. J. Mol. Sci. 2022, 23(9), 4624; https://doi.org/10.3390/ijms23094624 - 21 Apr 2022

Cited by 4 | Viewed by 2934

Abstract

Chromosomal rearrangements leading to the relocation of proto-oncogenes into transcription-active regions are found in various types of tumors. In particular, the transfer of proto-oncogenes to the locus of heavy chains of immunoglobulins (IGH) is frequently observed in B-lymphomas. The increased expression of the [...] Read more.

Chromosomal rearrangements leading to the relocation of proto-oncogenes into transcription-active regions are found in various types of tumors. In particular, the transfer of proto-oncogenes to the locus of heavy chains of immunoglobulins (IGH) is frequently observed in B-lymphomas. The increased expression of the MYC proto-oncogene due to IGH/MYC translocation is detected in approximately 85% of Burkitt lymphoma cases. The regulatory mechanisms affecting the oncogenes upon translocation include non-coding enhancer RNAs (eRNAs). We conducted a search for the eRNAs that may affect MYC transcription in the case of IGH/MYC translocation in Burkitt lymphoma, looking for potentially oncogenic eRNAs located at the IGH locus and predominantly expressed in B cells. Overexpression and knockdown of our primary candidate eRNA AL928768.3 led to the corresponding changes in the expression of MYC proto-oncogene in Burkitt lymphoma cells. Furthermore, we demonstrated that AL928768.3 knockdown decreased lymphoma cell proliferation and resistance to chemotherapy. Significant effects were observed only in cell lines bearing IGH/MYC abnormality but not in B-cell lines without this translocation nor primary B-cells. Our results indicate that AL928768.3 plays an important role in the development of Burkitt’s lymphoma and suggest it and similar, yet undiscovered eRNAs as potential tissue-specific targets for cancer treatment. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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Review

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15 pages, 1431 KiB

Open AccessReview

nc886, an RNA Polymerase III-Transcribed Noncoding RNA Whose Expression Is Dynamic and Regulated by Intriguing Mechanisms

by Yeon-Su Lee and Yong Sun Lee

Int. J. Mol. Sci. 2023, 24(10), 8533; https://doi.org/10.3390/ijms24108533 - 10 May 2023

Cited by 2 | Viewed by 1310

Abstract

nc886 is a medium-sized non-coding RNA that is transcribed by RNA polymerase III (Pol III) and plays diverse roles in tumorigenesis, innate immunity, and other cellular processes. Although Pol III-transcribed ncRNAs were previously thought to be expressed constitutively, this concept is evolving, and [...] Read more.

nc886 is a medium-sized non-coding RNA that is transcribed by RNA polymerase III (Pol III) and plays diverse roles in tumorigenesis, innate immunity, and other cellular processes. Although Pol III-transcribed ncRNAs were previously thought to be expressed constitutively, this concept is evolving, and nc886 is the most notable example. The transcription of nc886 in a cell, as well as in human individuals, is controlled by multiple mechanisms, including its promoter CpG DNA methylation and transcription factor activity. Additionally, the RNA instability of nc886 contributes to its highly variable steady-state expression levels in a given situation. This comprehensive review discusses nc886’s variable expression in physiological and pathological conditions and critically examines the regulatory factors that determine its expression levels. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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18 pages, 1143 KiB

Open AccessReview

Circular RNAs: Biogenesis, Biological Functions, and Roles in Myocardial Infarction

by Jialei Li, Yu Han, Shuang Wang, Xiaolei Wu, Jimin Cao and Teng Sun

Int. J. Mol. Sci. 2023, 24(4), 4233; https://doi.org/10.3390/ijms24044233 - 20 Feb 2023

Cited by 9 | Viewed by 2711

Abstract

Non-coding RNAs have been excavated as important cardiac function modulators and linked to heart diseases. Significant advances have been obtained in illuminating the effects of microRNAs and long non-coding RNAs. Nevertheless, the characteristics of circular RNAs are rarely mined. Circular RNAs (circRNAs) are [...] Read more.

Non-coding RNAs have been excavated as important cardiac function modulators and linked to heart diseases. Significant advances have been obtained in illuminating the effects of microRNAs and long non-coding RNAs. Nevertheless, the characteristics of circular RNAs are rarely mined. Circular RNAs (circRNAs) are widely believed to participate in cardiac pathologic processes, especially in myocardial infarction. In this review, we round up the biogenesis of circRNAs, briefly describe their biological functions, and summarize the latest literature on multifarious circRNAs related to new therapies and biomarkers for myocardial infarction. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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16 pages, 5986 KiB

Open AccessReview

Gene Network Analysis of the Transcriptome Impact of SARS-CoV-2 Interacting MicroRNAs in COVID-19 Disease

by Alexandra Ioana Moatar, Aimee Rodica Chis, Catalin Marian and Ioan-Ovidiu Sirbu

Int. J. Mol. Sci. 2022, 23(16), 9239; https://doi.org/10.3390/ijms23169239 - 17 Aug 2022

Cited by 8 | Viewed by 1931

Abstract

According to the World Health Organization (WHO), as of June 2022, over 536 million confirmed COVID-19 disease cases and over 6.3 million deaths had been globally reported. COVID-19 is a multiorgan disease involving multiple intricated pathological mechanisms translated into clinical, biochemical, and molecular [...] Read more.

According to the World Health Organization (WHO), as of June 2022, over 536 million confirmed COVID-19 disease cases and over 6.3 million deaths had been globally reported. COVID-19 is a multiorgan disease involving multiple intricated pathological mechanisms translated into clinical, biochemical, and molecular changes, including microRNAs. MicroRNAs are essential post-transcriptional regulators of gene expression, being involved in the modulation of most biological processes. In this study, we characterized the biological impact of SARS-CoV-2 interacting microRNAs differentially expressed in COVID-19 disease by analyzing their impact on five distinct tissue transcriptomes. To this end, we identified the microRNAs’ predicted targets within the list of differentially expressed genes (DEGs) in tissues affected by high loads of SARS-CoV-2 virus. Next, we submitted the tissue-specific lists of the predicted microRNA-targeted DEGs to gene network functional enrichment analysis. Our data show that the upregulated microRNAs control processes such as mitochondrial respiration and cytokine and cell surface receptor signaling pathways in the heart, lymph node, and kidneys. In contrast, downregulated microRNAs are primarily involved in processes related to the mitotic cell cycle in the heart, lung, and kidneys. Our study provides the first exploratory, systematic look into the biological impact of the microRNAs associated with COVID-19, providing a new perspective for understanding its multiorgan physiopathology. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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15 pages, 1760 KiB

Open AccessReview

Genomic Analyses of Non-Coding RNAs Overlapping Transposable Elements and Its Implication to Human Diseases

by Eun Gyung Park, Hongseok Ha, Du Hyeong Lee, Woo Ryung Kim, Yun Ju Lee, Woo Hyeon Bae and Heui-Soo Kim

Int. J. Mol. Sci. 2022, 23(16), 8950; https://doi.org/10.3390/ijms23168950 - 11 Aug 2022

Cited by 8 | Viewed by 2162

Abstract

It is estimated that up to 80% of the human genome is transcribed into RNA molecules but less than 2% of the genome encodes the proteins, and the rest of the RNA transcripts that are not translated into protein are called non-coding RNAs [...] Read more.

It is estimated that up to 80% of the human genome is transcribed into RNA molecules but less than 2% of the genome encodes the proteins, and the rest of the RNA transcripts that are not translated into protein are called non-coding RNAs (ncRNAs). Many studies have revealed that ncRNAs have biochemical activities as epigenetic regulators at the post-transcriptional level. Growing evidence has demonstrated that transposable elements (TEs) contribute to a large percentage of ncRNAs’ transcription. The TEs inserted into certain parts of the genome can act as alternative promoters, enhancers, and insulators, and the accumulation of TEs increases genetic diversity in the human genome. The TEs can also generate microRNAs, so-called miRNA-derived from transposable elements (MDTEs), and are also implicated in disease progression, such as infectious diseases and cancer. Here, we analyzed the origin of ncRNAs and reviewed the published literature on MDTEs related to disease progression. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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17 pages, 1792 KiB

Open AccessReview

MicroRNAs in Inflammatory Bowel Disease and Its Complications

by Srikruthi S. Krishnachaitanya, Max Liu, Ken Fujise and Qingjie Li

Int. J. Mol. Sci. 2022, 23(15), 8751; https://doi.org/10.3390/ijms23158751 - 06 Aug 2022

Cited by 12 | Viewed by 4953

Abstract

Inflammatory bowel disease (IBD), classified primarily between Crohn’s disease and ulcerative colitis, is a collection of chronic gastrointestinal inflammatory conditions that cause multiple complications because of systemic alterations in the immune response. One major player is microRNA (miRNA), which is found to be [...] Read more.

Inflammatory bowel disease (IBD), classified primarily between Crohn’s disease and ulcerative colitis, is a collection of chronic gastrointestinal inflammatory conditions that cause multiple complications because of systemic alterations in the immune response. One major player is microRNA (miRNA), which is found to be associated with multiple pathways in mediating inflammation, especially those of a chronic nature in IBD, as well as irritable bowel syndrome. Although there have been studies linking miRNA alterations in IBD, even differentiating Crohn’s disease and ulcerative colitis, this review focuses mainly on how miRNAs cause and mechanistically influence the pathologic complications of IBD. In addition to its role in the well-known progression towards colorectal cancer, we also emphasize how miRNA manifests the many extraintestinal complications in IBD such as cardiovascular diseases; neuropsychiatric conditions such as depression and anxiety disorders; and others, including various musculoskeletal, dermatologic, ocular, and hepatobiliary complications. We conclude through a description of its potential use in bettering diagnostics and the future treatment of IBD and its systemic symptoms. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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18 pages, 1358 KiB

Open AccessReview

Clinical Perspectives of Non-Coding RNA in Oral Inflammatory Diseases and Neuropathic Pain: A Narrative Review

by Jelena Roganović and Nina Petrović

Int. J. Mol. Sci. 2022, 23(15), 8278; https://doi.org/10.3390/ijms23158278 - 27 Jul 2022

Cited by 4 | Viewed by 2055

Abstract

Non-coding RNAs (ncRNAs) represent a research hotspot by playing a key role in epigenetic and transcriptional regulation of diverse biological functions and due to their involvement in different diseases, including oral inflammatory diseases. Based on ncRNAs’ suitability for salivary biomarkers and their involvement [...] Read more.

Non-coding RNAs (ncRNAs) represent a research hotspot by playing a key role in epigenetic and transcriptional regulation of diverse biological functions and due to their involvement in different diseases, including oral inflammatory diseases. Based on ncRNAs’ suitability for salivary biomarkers and their involvement in neuropathic pain and tissue regeneration signaling pathways, the present narrative review aims to highlight the potential clinical applications of ncRNAs in oral inflammatory diseases, with an emphasis on salivary diagnostics, regenerative dentistry, and precision medicine for neuropathic orofacial pain. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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23 pages, 1870 KiB

Open AccessReview

Roles of microRNAs and Long Non-Coding RNAs Encoded by Parasitic Helminths in Human Carcinogenesis

by Ana Gabriela Leija-Montoya, Javier González-Ramírez, Gustavo Martínez-Coronilla, María Esther Mejía-León, Mario Isiordia-Espinoza, Fausto Sánchez-Muñoz, Elda Georgina Chávez-Cortez, Viviana Pitones-Rubio and Nicolas Serafín-Higuera

Int. J. Mol. Sci. 2022, 23(15), 8173; https://doi.org/10.3390/ijms23158173 - 25 Jul 2022

Cited by 4 | Viewed by 3585

Abstract

Infectious agents such as viruses, bacteria, and parasites can lead to cancer development. Infection with the helminthic parasite Schistosoma haematobium can cause cancer of the urinary bladder in humans, and infection with the parasites Clonorchis sinensis and Opisthorchis viverrini can promote cholangiocarcinoma. These [...] Read more.

Infectious agents such as viruses, bacteria, and parasites can lead to cancer development. Infection with the helminthic parasite Schistosoma haematobium can cause cancer of the urinary bladder in humans, and infection with the parasites Clonorchis sinensis and Opisthorchis viverrini can promote cholangiocarcinoma. These three pathogens have been categorized as “group 1: carcinogenic to humans” by the International Agency for Research on Cancer (IARC). Additionally, the parasite Schistosoma japonicum has been associated with liver and colorectal cancer and classified as “group 2B: possibly carcinogenic to humans”. These parasites express regulatory non-coding RNAs as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which modulate genic expression in different biological processes. In this review, we discuss the potential roles of miRNAS and lncRNAs encoded by helminthic parasites that are classified by the IARC as carcinogenic and possibly carcinogenic to humans. The miRNAs of these parasites may be involved in carcinogenesis by modulating the biological functions of the pathogen and the host and by altering microenvironments prone to tumor growth. miRNAs were identified in different host fluids. Additionally, some miRNAs showed direct antitumoral effects. Together, these miRNAs show potential for use in future therapeutic and diagnostic applications. LncRNAs have been less studied in these parasites, and their biological effects in the parasite–host interaction are largely unknown. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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18 pages, 2200 KiB

Open AccessReview

Role of miRNAs in Human T Cell Leukemia Virus Type 1 Induced T Cell Leukemia: A Literature Review and Bioinformatics Approach

by Caio Bezerra Machado, Leidivan Sousa da Cunha, Jersey Heitor da Silva Maués, Flávia Melo Cunha de Pinho Pessoa, Marcelo Braga de Oliveira, Rodrigo Monteiro Ribeiro, Germison Silva Lopes, Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, André Salim Khayat and Caroline Aquino Moreira-Nunes

Int. J. Mol. Sci. 2022, 23(10), 5486; https://doi.org/10.3390/ijms23105486 - 14 May 2022

Cited by 5 | Viewed by 2845

Abstract

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming [...] Read more.

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients’ samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-β, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs’ roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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18 pages, 1385 KiB

Open AccessReview

Non-Coding RNAs Regulate Spontaneous Abortion: A Global Network and System Perspective

by Jianyu Gan, Ting Gu, Huaqiang Yang, Zheng Ao, Gengyuan Cai, Linjun Hong and Zhenfang Wu

Int. J. Mol. Sci. 2022, 23(8), 4214; https://doi.org/10.3390/ijms23084214 - 11 Apr 2022

Cited by 8 | Viewed by 3060

Abstract

Spontaneous abortion is a common pregnancy complication that negatively impacts women’s health and commercial pig production. It has been demonstrated that non-coding RNA (ncRNA) is involved in SA by affecting cell proliferation, invasion, apoptosis, epithelial-mesenchymal transformation (EMT), migration, and immune response. Over the [...] Read more.

Spontaneous abortion is a common pregnancy complication that negatively impacts women’s health and commercial pig production. It has been demonstrated that non-coding RNA (ncRNA) is involved in SA by affecting cell proliferation, invasion, apoptosis, epithelial-mesenchymal transformation (EMT), migration, and immune response. Over the last decade, research on ncRNAs in SA has primarily concentrated on micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In this review, we discuss recent ncRNA studies focused on the function and mechanism of miRNAs, lncRNAs, and circRNAs in regulating SA. Meanwhile, we suggest that a ceRNA regulatory network exists in the onset and development of SA. A deeper understanding of this network will accelerate the process of the quest for potential RNA markers for SA diagnosis and treatment. Full article

(This article belongs to the Special Issue Non-coding RNAs in Pathogens and Associated Diseases)

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