Functional long non-coding and circular RNAs in zebrafish

2021 ◽  
Author(s):  
Gyan Ranjan ◽  
Paras Sehgal ◽  
Disha Sharma ◽  
Vinod Scaria ◽  
Sridhar Sivasubbu
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cellular Level ◽  
Model Organisms ◽  
Circular Rnas ◽  
Computational Techniques ◽  
Modeling And Analysis ◽  
Novel Transcript ◽  
Disease Biology ◽  
Analysis Of Function

AbstractThe utility of model organisms to understand the function of a novel transcript/genes has allowed us to delineate their molecular mechanisms in maintaining cellular homeostasis. Organisms such as zebrafish have contributed a lot in the field of developmental and disease biology. Attributable to advancement and deep transcriptomics, many new transcript isoforms and non-coding RNAs such as long noncoding RNA (lncRNA) and circular RNAs (circRNAs) have been identified and cataloged in multiple databases and many more are yet to be identified. Various methods and tools have been utilized to identify lncRNAs/circRNAs in zebrafish using deep sequencing of transcriptomes as templates. Functional analysis of a few candidates such as tie1-AS, ECAL1 and CDR1as in zebrafish provides a prospective outline to approach other known or novel lncRNA/circRNA. New genetic alteration tools like TALENS and CRISPRs have helped in probing for the molecular function of lncRNA/circRNA in zebrafish. Further latest improvements in experimental and computational techniques offer the identification of lncRNA/circRNA counterparts in humans and zebrafish thereby allowing easy modeling and analysis of function at cellular level.

scholarly journals Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis

2021 ◽  
Vol 8 (12) ◽  
pp. 170
Author(s):  
Alexandra V. Rozhkova ◽  
Veronika G. Dmitrieva ◽  
Elena V. Nosova ◽  
Alexander D. Dergunov ◽  
Svetlana A. Limborska ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Gene Promoter ◽  
High Density Lipoproteins ◽  
Circular Rnas ◽  
Promoter Regions ◽  
Genomic Variants ◽  
Transcription Activators ◽  
And Function

Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. This review summarizes the progress in studying the genomic variants of ABCA1, ABCG1, and SCARB1, and the regulation of their function at transcriptional and post-transcriptional levels in atherosclerosis. Defects in the structure and function of ABCA1, ABCG1, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs. The potential biomarkers and targets for atheroprotection, based on molecular mechanisms of expression regulation for three transporter genes, are also discussed in this review.

scholarly journals Circular RNAs: Biogenesis, Mechanism, and Function in Human Cancers

2019 ◽  
Vol 20 (16) ◽  
pp. 3926 ◽  
Author(s):  
Xing Zhao ◽  
Yujie Cai ◽  
Jianzhen Xu
Keyword(s):  
Noncoding Rna ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cancer Development ◽  
Circular Rnas ◽  
Open Questions ◽  
Circular Configuration ◽  
And Function

CircRNAs are a class of noncoding RNA species with a circular configuration that is formed by either typical spliceosome-mediated or lariat-type splicing. The expression of circRNAs is usually abnormal in many cancers. Several circRNAs have been demonstrated to play important roles in carcinogenesis. In this review, we will first provide an introduction of circRNAs biogenesis, especially the regulation of circRNA by RNA-binding proteins, then we will focus on the recent findings of circRNA molecular mechanisms and functions in cancer development. Finally, some open questions are also discussed.

scholarly journals circAkap17b acts as a miR-7 family molecular sponge to regulate FSH secretion in rat pituitary cells

2020 ◽  
Vol 65 (4) ◽  
pp. 135-148
Author(s):  
Chang-Jiang Wang ◽  
Fei Gao ◽  
Yi-Jie Huang ◽  
Dong-Xu Han ◽  
Yi Zheng ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Pituitary Cells ◽  
Rat Pituitary ◽  
Rna Immunoprecipitation ◽  
Rat Pituitary Cells

The pituitary gland functions as a prominent regulator of diverse physiologic processes by secreting multiple hormones. Circular RNAs (circRNAs) are an emerging novel type of endogenous noncoding RNA that have recently been recognized as powerful regulators participating in various biological processes. However, the physiological roles and molecular mechanisms of circRNAs in pituitary remain largely unclear. Herein, we concentrated on expounding the biological function and molecular mechanism of circRNA in rat pituitary. In this study, we identified a novel circRNA in pituitary tissue, circAkap17b, which was pituitary- and stage-specific. Then, we designed circAkap17b siRNA and constructed an overexpression plasmid to evaluate the effect of loss- and gain-of-circAkap17b function on FSH secretion. Interestingly, silencing circAkakp17b significantly inhibited FSH expression and secretion, while overexpression of circAkap17b enhanced FSH expression and secretion. Furthermore, dual luciferase reporter and RNA immunoprecipitation (RIP) assays confirmed that circAkap17b could serve as miR-7 sponge to regulate target genes. Additionally, miR-7b suppressed FSH expression and secretion by directly targeting Fshb through the dual luciferase reporter and RT-qPCR analysis. Additionally, rescue experiments showed that circAkap17b could regulate FSH secretion in pituitary cells through a circAkap17b-miR-7-Fshb axis. Collectively, we demonstrated that circAkap17b could act as a molecular sponge of miR-7 to upregulate expression of the target gene Fshb and facilitate FSH secretion. These findings provide evidence for a novel regulatory role of circRNAs in pituitary.

scholarly journals CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

2020 ◽  
Author(s):  
Hanchen Xu ◽  
Yujing Liu ◽  
Peiqiu Cheng ◽  
Chunyan Wang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Expression Profile ◽  
High Throughput ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Malignant Progression ◽  
Circular Rnas

Abstract Background: Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer.Methods: The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms.Results: CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA­_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells.Conclusions: CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.

Circular RNAs emerge as important regulators with great potential for clinical application in gastric cancer

2021 ◽  
Vol 15 (1) ◽  
pp. 69-82
Author(s):  
Mei Wang ◽  
Zheng Gong ◽  
Xinxin Zhao ◽  
Wanjun Yu ◽  
Feng Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Basic Knowledge ◽  
Research Progress ◽  
Future Research ◽  
Circular Rnas ◽  
Research Directions ◽  
Potential Applications ◽  
Future Research Directions

Gastric cancer (GC) is a common digestive malignancy with a high-ranking morbidity and mortality. Therefore, it is urgent to identify novel indicators and develop new strategies for clinical diagnosis and treatment of GC. As a type of noncoding RNA, circular RNAs (circRNAs) have received increased attention in GC during recent years. To more comprehensively understand current research progress on circRNAs in GC, in this review, we introduce basic knowledge of circRNAs, summarize abnormally expressed circRNAs and discuss their functions and regulatory molecular mechanisms in GC. Then, we review potential applications of circRNAs for GC diagnosis, prognosis and treatment. Finally, we conclude by highlighting major advancements of circRNAs in GC research, and we discuss existing challenges and possible future research directions of GC-associated circRNAs.

scholarly journals CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Hanchen Xu ◽  
Yujing Liu ◽  
Peiqiu Cheng ◽  
Chunyan Wang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Expression Profile ◽  
High Throughput ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Malignant Progression ◽  
Circular Rnas

Abstract Background Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer. Methods The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms. Results CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells. Conclusions CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.

Radio-Susceptibility of Nasopharyngeal Carcinoma: Focus on Epstein- Barr Virus, MicroRNAs, Long Non-Coding RNAs and Circular RNAs

2020 ◽  
Vol 13 (3) ◽  
pp. 192-205 ◽  
Author(s):  
Fanghong Lei ◽  
Tongda Lei ◽  
Yun Huang ◽  
Mingxiu Yang ◽  
Mingchu Liao ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Regulatory Networks ◽  
Epstein Barr Virus ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Circular Rnas ◽  
Barr Virus ◽  
Non Coding Rnas ◽  
Epstein Barr

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. As a neoplastic disorder, NPC is a highly malignant squamous cell carcinoma that is derived from the nasopharyngeal epithelium. NPC is radiosensitive; radiotherapy or radiotherapy combining with chemotherapy are the main treatment strategies. However, both modalities are usually accompanied by complications and acquired resistance to radiotherapy is a significant impediment to effective NPC therapy. Therefore, there is an urgent need to discover effective radio-sensitization and radio-resistance biomarkers for NPC. Recent studies have shown that Epstein-Barr virus (EBV)-encoded products, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which share several common signaling pathways, can function in radio-related NPC cells or tissues. Understanding these interconnected regulatory networks will reveal the details of NPC radiation sensitivity and resistance. In this review, we discuss and summarize the specific molecular mechanisms of NPC radio-sensitization and radio-resistance, focusing on EBV-encoded products, miRNAs, lncRNAs and circRNAs. This will provide a foundation for the discovery of more accurate, effective and specific markers related to NPC radiotherapy. EBVencoded products, miRNAs, lncRNAs and circRNAs have emerged as crucial molecules mediating the radio-susceptibility of NPC. This understanding will improve the clinical application of markers and inform the development of novel therapeutics for NPC.

scholarly journals Knockdown of Circ_SLC39A8 protects against the progression of osteoarthritis by regulating miR-591/IRAK3 axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jizhe Yu ◽  
Yushuang Qin ◽  
Naxin Zhou
Keyword(s):  
Cell Viability ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Oa Chondrocytes ◽  
Polymerase Chain ◽  
Apoptosis And Inflammation ◽  
The Relationship

Abstract Background The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases, including osteoarthritis (OA). The purpose of this study was to identify the role and mechanism of circ_SLC39A8 in regulating the progression of OA. Methods The expression levels of circ_SLC39A8, miR-591, and its potential target gene, interleukin-1-receptor-associated kinase 3 (IRAK3), were identified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The relationship between miR-591 and circ_SLC39A8 or IRAK3 was predicted by bioinformatics tools and verified by dual-luciferase reporter. Results Circ_SLC39A8 and IRAK3 were upregulated and miR-591 was downregulated in OA cartilage tissues. Knockdown of circ_SLC39A8 inhibited apoptosis and inflammation in OA chondrocytes, while these effects were reversed by downregulating miR-591. Promotion cell viability effects of miR-591 were partially reversed by IRAK3 overexpression. Conclusion Our findings indicated that knockdown of circ_SLC39A8 delayed the progression of OA via modulating the miR-591-IRAK3 axis, providing new insight into the molecular mechanisms of OA pathogenesis.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

scholarly journals Small Non-Coding-RNA in Gynecological Malignancies

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1085
Author(s):  
Shailendra Kumar Dhar Dwivedi ◽  
Geeta Rao ◽  
Anindya Dey ◽  
Priyabrata Mukherjee ◽  
Jonathan D. Wren ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
P Element ◽  
Gynecologic Malignancies ◽  
Diagnosis And Prognosis ◽  
Gynecological Malignancies ◽  
Non Coding Rna ◽  
Therapeutic Research ◽  
Regulatory Functions

Gynecologic malignancies, which include cancers of the cervix, ovary, uterus, vulva, vagina, and fallopian tube, are among the leading causes of female mortality worldwide, with the most prevalent being endometrial, ovarian, and cervical cancer. Gynecologic malignancies are complex, heterogeneous diseases, and despite extensive research efforts, the molecular mechanisms underlying their development and pathology remain largely unclear. Currently, mechanistic and therapeutic research in cancer is largely focused on protein targets that are encoded by about 1% of the human genome. Our current understanding of 99% of the genome, which includes noncoding RNA, is limited. The discovery of tens of thousands of noncoding RNAs (ncRNAs), possessing either structural or regulatory functions, has fundamentally altered our understanding of genetics, physiology, pathophysiology, and disease treatment as they relate to gynecologic malignancies. In recent years, it has become clear that ncRNAs are relatively stable, and can serve as biomarkers for cancer diagnosis and prognosis, as well as guide therapy choices. Here we discuss the role of small non-coding RNAs, i.e., microRNAs (miRs), P-Element induced wimpy testis interacting (PIWI) RNAs (piRNAs), and tRNA-derived small RNAs in gynecological malignancies, specifically focusing on ovarian, endometrial, and cervical cancer.

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