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Digestive Diseases and Sciences Feb 2021Gastric cancer (GC) is one of the most commonly diagnosed malignancy worldwide. DLX6 antisense RNA 1 (DLX6-AS1) is a long noncoding RNA (lncRNA) that exhibits oncogenic...
BACKGROUND
Gastric cancer (GC) is one of the most commonly diagnosed malignancy worldwide. DLX6 antisense RNA 1 (DLX6-AS1) is a long noncoding RNA (lncRNA) that exhibits oncogenic effects on multiple human carcinomas.
AIMS
This study aimed to investigate the regulatory effect of DLX6-AS1 in GC progression.
METHODS
The expression of DLX6-AS1 in GC tissues and cell lines was examined. The cell viability, number of clones, and apoptosis, aerobic glycolysis, and mitochondrial respiration was assessed. The effect of DLX6-AS1 on tumor growth in nude mice was also evaluated.
RESULTS
DLX6-AS1 was overexpressed in GC tissues and cell lines. DLX6-AS1 knockdown by short hairpin RNA (shRNA) significantly inhibited cell viability and colony formation, and induced apoptosis. DLX6-AS1 silencing impaired aerobic glycolysis but stimulated mitochondrial respiration in GC cells. miR-4290 was confirmed as a downstream target of DLX6-AS1, and their expression levels were inversely correlated. GC cells expressing sh-DLX6-AS1 showed significantly lower level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), a target of miR-4290, compared to cells expressing control shRNA. In addition, the suppressed GC cell malignancy upon DLX6-AS1 knockdown could be prominently reversed by PDK1 overexpression. Meanwhile, PDK1 overexpression enhanced aerobic glycolysis but repressed mitochondrial respiration under sh-DLX6-AS1 treatment. Furthermore, DLX6-AS1 knockdown significantly delayed the tumor growth in a mouse xenograft model inoculated with GC cells.
CONCLUSIONS
LncRNA DLX6-AS1 regulated tumor growth and aerobic glycolysis in GC by targeting miR-4290 and PDK1, suggesting DLX6-AS1 might serve as a novel potential therapeutic target for GC treatment from bench to clinic.
Topics: Animals; Cell Line, Tumor; Cell Proliferation; Glucose; Homeodomain Proteins; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; RNA, Antisense; Stomach Neoplasms; Xenograft Model Antitumor Assays
PubMed: 32239379
DOI: 10.1007/s10620-020-06223-4 -
Pathology, Research and Practice Jun 2023MAGI2 Antisense RNA 3 (MAGI2-AS3) is a long non-coding RNA (lncRNA) transcribed from a locus on 7q21.11. This lncRNA has been described to be abnormally expressed in a... (Review)
Review
MAGI2 Antisense RNA 3 (MAGI2-AS3) is a long non-coding RNA (lncRNA) transcribed from a locus on 7q21.11. This lncRNA has been described to be abnormally expressed in a variety of malignancies in correlation with many clinical characteristics. Moreover, it might participate in the pathogenesis of congenital diaphragmatic hernia, Alzheimer's disease and intervertebral disc degeneration. Mechanistically, MAGI2-AS3 can serve as a molecular sponge for miR-142-3p, miR-424-5p, miR-15b, miR-233, miR-452-5p, miR-629-5p, miR-25, miR-155, miR-23a-3p, miR-519c-3p, miR-374b-5p, miR-374a, miR-31-5p, miR-3163, miR-525-5p, miR-15-5p, miR-374a-5p, miR-374b-5p, miR-218-5p, miR-141-3p and miR-200a-3p to regulate expression of their mRNA targets. The current review summarizes the role of MAGI2-AS3 in different disorders to highlight its importance in their pathophysiology.
Topics: Humans; Adaptor Proteins, Signal Transducing; Cell Proliferation; Guanylate Kinases; MicroRNAs; RNA, Long Noncoding; RNA, Antisense
PubMed: 37196468
DOI: 10.1016/j.prp.2023.154530 -
Molecular Therapy : the Journal of the... Jun 2023Circular RNAs (circRNAs) are a group of non-coding RNAs with a unique circular structure generated by back-splicing. It is acknowledged that circRNAs play critical roles...
Circular RNAs (circRNAs) are a group of non-coding RNAs with a unique circular structure generated by back-splicing. It is acknowledged that circRNAs play critical roles in cardiovascular diseases. However, functional studies of circRNAs were impeded due to lack of effective in vivo silencing approaches. Since most circRNAs are produced by protein-coding transcripts, gene editing typically affects the coding activity of the parental genes. In this study, we developed a circular antisense RNA (cA-circSlc8a1) that could silence the highly expressed circRNA circSlc8a1 in the mouse heart but not its parental Slc8a1 linear mRNA. Transgenic cA-circSlc8a1 mice developed congestive heart failure resulting in a significant increase in the body weight secondary to peripheral edema and congestive hepatopathy. To further test the role of circSlc8a1, we generated transgenic mice overexpressing circSlc8a1 and observed a protective effect of circSlc8a1 in a pressure overload model. Mechanistically, we found that circSlc8a1 translocated into mitochondria to drive ATP synthesis. While establishing a transgenic murine model for antisense-mediated circRNA silencing without interfering with the parental linear RNA, our finding revealed the essential role of circSlc8a1 in maintaining heart function and may lay the groundwork of using the circular antisense RNA as a potential gene therapy approach for cardiovascular diseases.
Topics: Animals; Mice; Cardiovascular Diseases; Heart Failure; RNA, Antisense; RNA, Circular; RNA, Messenger; Sodium-Calcium Exchanger
PubMed: 36245125
DOI: 10.1016/j.ymthe.2022.10.005 -
Biochimie Sep 2019Prokaryotes encounter constant and often brutal modifications to their environment. In order to survive, they need to maintain fitness, which includes adapting their... (Review)
Review
Prokaryotes encounter constant and often brutal modifications to their environment. In order to survive, they need to maintain fitness, which includes adapting their protein expression patterns. Many factors control gene expression but this review focuses on just one, namely antisense RNAs (asRNAs), a class of non-coding RNAs (ncRNAs) characterized by their location in cis and their perfect complementarity with their targets. asRNAs were considered for a long time to be trivial and only to be found on mobile genetic elements. However, recent advances in methodology have revealed that their abundance and potential activities have been underestimated. This review aims to illustrate the role of asRNA in various physiologically crucial functions in both archaea and bacteria, which can be regrouped in three categories: cell maintenance, horizontal gene transfer and virulence. A literature survey of asRNAs demonstrates the difficulties to characterize and assign a role to asRNAs. With the aim of facilitating this task, we describe recent technological advances that could be of interest to identify new asRNAs and to discover their function.
Topics: Archaea; Bacteria; Bacterial Physiological Phenomena; Gene Expression Regulation, Archaeal; Gene Expression Regulation, Bacterial; Gene Transfer, Horizontal; RNA, Antisense; RNA, Archaeal; RNA, Bacterial; Virulence
PubMed: 30995539
DOI: 10.1016/j.biochi.2019.04.015 -
RNA (New York, N.Y.) Dec 2021Type I toxin-antitoxin (T1TA) systems constitute a large class of genetic modules with antisense RNA (asRNA)-mediated regulation of gene expression. They are widespread...
Type I toxin-antitoxin (T1TA) systems constitute a large class of genetic modules with antisense RNA (asRNA)-mediated regulation of gene expression. They are widespread in bacteria and consist of an mRNA coding for a toxic protein and a noncoding asRNA that acts as an antitoxin preventing the synthesis of the toxin by directly base-pairing to its cognate mRNA. The co- and post-transcriptional regulation of T1TA systems is intimately linked to RNA sequence and structure, therefore it is essential to have an accurate annotation of the mRNA and asRNA molecules to understand this regulation. However, most T1TA systems have been identified by means of bioinformatic analyses solely based on the toxin protein sequences, and there is no central repository of information on their specific RNA features. Here we present the first database dedicated to type I TA systems, named T1TAdb. It is an open-access web database (https://d-lab.arna.cnrs.fr/t1tadb) with a collection of ∼1900 loci in ∼500 bacterial strains in which a toxin-coding sequence has been previously identified. RNA molecules were annotated with a bioinformatic procedure based on key determinants of the mRNA structure and the genetic organization of the T1TA loci. Besides RNA and protein secondary structure predictions, T1TAdb also identifies promoter, ribosome-binding, and mRNA-asRNA interaction sites. It also includes tools for comparative analysis, such as sequence similarity search and computation of structural multiple alignments, which are annotated with covariation information. To our knowledge, T1TAdb represents the largest collection of features, sequences, and structural annotations on this class of genetic modules.
Topics: Antitoxins; Bacterial Proteins; Computational Biology; Databases, Genetic; Gene Expression Regulation, Bacterial; RNA, Antisense; Toxin-Antitoxin Systems
PubMed: 34531327
DOI: 10.1261/rna.078802.121 -
Bioengineered Apr 2022Endometriosis is an estrogen-dependent chronic gynecological syndrome. Recent studies have shown that long non-coding RNAs participate in the pathogenesis and...
Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression.
Endometriosis is an estrogen-dependent chronic gynecological syndrome. Recent studies have shown that long non-coding RNAs participate in the pathogenesis and development of endometriosis. This study aimed to explore the mechanisms of DHRS4 antisense RNA 1 (DHRS4-AS1) in endometriosis. Dual-luciferase reporter assays were conducted to determine the relationship between DHRS4-AS1, microRNA (miR)-139-5p, and arrestin domain-containing 3 (ARRDC3). Furthermore, the expression of DHRS4-AS1 and miR-139-5p in ectopic endometrial stromal cells (EC-ESCs) and endometriosis tissues was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and Transwell assays were performed to evaluate the proliferation, apoptosis, and migration and invasion of EC-ESCs, respectively. Western blotting and RT-qPCR were further utilized to determine cleaved-Caspase 3, Caspase 3, and matrix metalloproteinase 9 (MMP-9) expression levels. Compared with the EN group, DHRS4-AS1 levels were lower and miR-139-5p levels were higher in EC-ESCs and tissues obtained from patients with endometriosis. Functional assays validated that DHRS4-AS1 targets miR-139-5p, with ARRDC3 being a downstream target of miR-139-5p. Rescue experiments demonstrated that DHRS4-AS1 inhibited EC-ESC proliferation, migration, and invasion, but promoted apoptosis, by targeting miR-139-5p in endometriosis. cleaved-Caspase3 expression level and the cleaved-Caspase 3/Caspase 3 ratio increased, while the expression levels of MMP-9 decreased, after transfection with DHRS4-AS1 overexpression plasmids; however, the effects induced by DHRS4-AS1 overexpression could be partially reversed by co-transfection with the miR-139-5p mimic. The current study demonstrates that the DHRS4-AS1/miR-139-5p/ARRDC3 axis participates in the regulation of EC-ESC function.
Topics: Caspase 3; Cell Line, Tumor; Cell Movement; Cell Proliferation; Endometriosis; Female; Humans; Matrix Metalloproteinase 9; MicroRNAs; Oxidoreductases; RNA, Antisense; RNA, Long Noncoding
PubMed: 35414313
DOI: 10.1080/21655979.2022.2060781 -
Life Sciences Jan 2020Long noncoding RNA melanotransferrin antisense RNA (MFI2-AS1) plays a vital role in the development of multiple diseases. This study aimed to investigate the effect of... (Review)
Review
AIMS
Long noncoding RNA melanotransferrin antisense RNA (MFI2-AS1) plays a vital role in the development of multiple diseases. This study aimed to investigate the effect of this lncRNA on osteoarthritis progression and explore the interaction among MFI2-AS1, microRNA (miR)-130a-3p and transcription factor 4 (TCF4).
METHODS
Forty-six knee osteoarthritis tissues and 28 normal samples were collected. Human chondrocytes C28/I2 cells treated by lipopolysaccharide (LPS) were used as the model of osteoarthritis. The expression levels of MFI2-AS1, miR-130a-3p and TCF4 were detected by quantitative real-time polymerase chain reaction or western blot. LPS-induced chondrocytes injury was investigated by cell viability, apoptosis, inflammatory response and extracellular matrix degradation using MTT, flow cytometry, enzyme-linked immunosorbent assay and western blot. The target association between miR-130a-3p and MFI2-AS1 or TCF4 was confirmed by luciferase reporter assay and RNA immunoprecipitation.
RESULTS
MFI2-AS1 expression was increased in osteoarthritis tissues and LPS-treated C28/I2 cells. Silence of MFI2-AS1 attenuated LPS-induced viability suppression, apoptosis production, inflammatory response and extracellular matrix degradation. MFI2-AS1 was validated as a decoy of miR-130a-3p and TCF4 was confirmed as a target of miR-130a-3p. miR-130a-3p overexpression inhibited LPS-induced cell injury in C28/I2 cells by decreasing TCF4 expression. Moreover, knockdown of MFI2-AS1 alleviated LPS-induced cell injury in C28/I2 cells by mediating miR-130a-3p and TCF4.
CONCLUSION
Knockdown of MFI2-AS1 increased cell viability but suppressed apoptosis, inflammatory response and extracellular matrix degradation in LPS-treated chondrocytes by increasing miR-130a-3p and decreasing TCF4, indicating a novel target for the treatment of osteoarthritis.
Topics: Animals; Cell Line; Cell Proliferation; Cell Survival; Chondrocytes; Gene Knockdown Techniques; Humans; Lipopolysaccharides; MicroRNAs; Osteoarthritis; RNA, Antisense; RNA, Long Noncoding; Transcription Factor 4
PubMed: 31678554
DOI: 10.1016/j.lfs.2019.117019 -
Anti-cancer Drugs Jan 2022Long noncoding RNAs (lncRNAs) are one of the interesting fields in cancer researches. LncRNAs are generally dysregulated in many diseases. LMCD1 antisense RNA 1...
Long noncoding RNAs (lncRNAs) are one of the interesting fields in cancer researches. LncRNAs are generally dysregulated in many diseases. LMCD1 antisense RNA 1 (LMCD1-AS1) is a newly identified lncRNA with protumorigenic functions on tumor cells. LMCD1-AS1 expression is increased in hepatocellular carcinoma (HCC). LMCD1-AS1 is a sponge of miR-106b-5p activity. LMCD1-AS1 modulates the survival of osteosarcoma via targeting miR-106b-5p. LMCD1-AS1 and Sp1 are highly expressed in osteosarcoma. SP1 can bind to the promoter region of LMCD1-AS1, resulting in its overexpression in osteosarcoma. GLI2 is shown to bind to the LMCD1-AS1 promoter and is transcriptionally activated by LMCD1-AS1. LMCD1 acts as a miR-1287-5p sponge to increase GLI2 expression. LMCD1 is abundantly expressed in kidney tissue. Moreover, it is functionally involved in protein-protein interactions with transcriptional co-repressor activity, including regulation of the calcineurin-NFAT signaling cascade known to play a critical role in recovery from acute kidney injury (AKI). The E2F1/LMCD1-AS1/miR-345-5p/COL6A3 axis is a newly identified regulatory mechanism, which has a function in cholangiocarcinoma (CCA) tumorigenesis and progression and provides potential therapeutic targets for CCA. Also, LMCD1-AS1 functions in thyroid cancer (THCA) development. LMCD1-AS1 is overexpressed in THCA cells, and LMCD1-AS1 knockdown suppresses the malignant phenotypes of THCA cells. In THCA development, LMCD1-AS1 exerts protumorigenic function through sponging miR-1287-5p to increase GLI2 expression, constituting a feedback loop of LMCD1-AS1/miR-1287-5p/GLI2. In this review, the author focuses on the molecular mechanisms of newly identified long noncoding RNA LMCD1 antisense RNA 1 (LMCD1-AS1).
Topics: Acute Kidney Injury; Calcineurin; Carcinogenesis; Co-Repressor Proteins; Humans; Immunoglobulins; LIM Domain Proteins; MicroRNAs; NFATC Transcription Factors; Neoplasms; Nuclear Proteins; RNA, Antisense; RNA, Long Noncoding; Signal Transduction; Zinc Finger Protein Gli2
PubMed: 34232945
DOI: 10.1097/CAD.0000000000001124 -
Science China. Life Sciences Oct 2021Long non-coding RNAs (lncRNAs) have become a hotspot in biomedical research. This interest reflects their extensive involvement in the regulation of the expression of... (Review)
Review
Long non-coding RNAs (lncRNAs) have become a hotspot in biomedical research. This interest reflects their extensive involvement in the regulation of the expression of other genes, and their influence on the occurrence and development of a variety of human diseases. Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1) is a recently discovered oncogenic lncRNA. It is highly expressed in a variety of solid tumors, and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs, or by the direct binding to other proteins. Ultimately, AFAP1-AS1 promotes proliferation, chemotherapy resistance, and resistance to apoptosis, maintains stemness, and enhances invasion and migration of tumor cells. This paper summarizes the research concerning AFAP1-AS1 in malignant tumors, including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors. We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research. AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.
Topics: Biomarkers, Tumor; Carcinogenesis; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Microfilament Proteins; Neoplasms; RNA, Antisense; RNA, Long Noncoding; RNA-Binding Proteins; Up-Regulation
PubMed: 33999309
DOI: 10.1007/s11427-020-1874-6 -
Trends in Molecular Medicine Dec 2020RNA therapeutics are finally taking their place as a main drug category alongside small molecules and proteins. Here, we follow the twists and turns on their road to... (Review)
Review
RNA therapeutics are finally taking their place as a main drug category alongside small molecules and proteins. Here, we follow the twists and turns on their road to success and highlight areas of ongoing research.
Topics: Drug Development; Genetic Therapy; Humans; MicroRNAs; Oligonucleotides; RNA; RNA, Antisense; RNA, Small Interfering
PubMed: 32988738
DOI: 10.1016/j.molmed.2020.08.007