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Ma A, Sun Y, Ogbodu RO, Xiao L, Deng H, Zhou H. Identification of biomarkers of hepatocellular carcinoma gene prognosis based on the immune-related lncRNA signature of transcriptome data. Funct Integr Genomics 2023; 23:104. [PMID: 36976410 DOI: 10.1007/s10142-023-01019-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/06/2023] [Accepted: 03/08/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) are well established to have an important role in cancer. The goal of this research was to investigate the prognostic usefulness of putative immune-related lncRNAs in hepatocellular carcinoma (HCC). METHODS The developed lncRNA signature was validated using 343 HCC patients from The Cancer Genome Atlas (TCGA) and 81 samples from Gene Expression Omnibus (GEO). Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to analyze immune-related lncRNAs for HCC prognosis. Patients in the low-risk group survived substantially longer than those in the high-risk group (P < 0.05). The discovered signal might be a useful prognostic factor for predicting patient survival. Overall survival predicted some clinical net improvements, according to the nomogram. Numerous enrichment approaches (including gene set enrichment analysis) were utilized to investigate the underlying mechanisms. RESULTS Drug metabolism, mTOR, and p53 signaling pathways were associated with high-risk groups. When the expression of lncRNA PRRT3-AS1 was silenced in HepG2 cells, the proliferation, migration, and invasion abilities of HepG2 cells were decreased, and apoptosis was enhanced. In the supernatant from HepG2 cells with PRRT3-AS1 knockdown, the anti-inflammatory factors IL-10 and TGF-1 were induced, whereas the pro-inflammatory factors IL-1β, TNF-α, and IL-6 were reduced (P < 0.05). After PRRT3-AS1 knockdown, the protein expression of CD24, THY1, LYN, CD47, and TRAF2 in HepG2 cells was attenuated (P < 0.05). CONCLUSION The discovery of five immune-related lncRNA signatures has significant therapeutic significance for predicting patient prognosis and directing personalized treatment for patients with HCC, which requires additional prospective confirmation.
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Affiliation(s)
- Andi Ma
- Hunan University of Medicine School of Public Health and Laboratory Medicine, Huaihua, 418000, China
| | - Yukai Sun
- Max Delbruck Centrum fur Molekulare Medizin Experimental and Clinical Research Center (MDC), AG Translational Oncology of Solid Tumors, Robert-Rössle-Straße 10, 13125, Berlin, Germany
| | - Racheal O Ogbodu
- Institute of Physiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Ling Xiao
- Department of Histology and Embryology, School of Basic Medical Sciences, Central South University Xiangya School of Medicine, Changsha, 410013, China
| | - Haibin Deng
- Department of General Thoracic Surgery, Inselspital Universitatsspital Bern, Murtenstrasse 50, 3008, Bern, Swaziland
| | - Hui Zhou
- Department of Lymphoma and Hematology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, 410013, Hunan, China.
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Paredes O, Morales JA, Mendizabal AP, Romo-Vázquez R. Metacode: One code to rule them all. Biosystems 2021; 208:104486. [PMID: 34274462 DOI: 10.1016/j.biosystems.2021.104486] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 07/07/2021] [Accepted: 07/09/2021] [Indexed: 12/13/2022]
Abstract
The code of codes or metacode is a microcosm where biological layers, as well as their codes, interact together allowing the continuity of information flow in organisms by increasing biological entities' complexity. Through this novel organic code, biological systems scale towards niches with higher informatic freedom building structures that increase the entropy in the universe. Code biology has developed a novel informational framework where biological entities strive themselves through the information flow carried out through organic codes consisting of two molecular or functional landscapes intertwined through arbitrary linkages via an adaptor whose nature is autonomous from molecular determinism. Here we will integrate genomic and epigenomic codes according to the evidence released in ENCODE (phase 3), psychENCODE and GTEx project, outlining the principles of the metacode, to address the continuous nature of biological systems and their inter-layered information flow. This novel complex metacode maps from very constrained sets of elements (i.e., regulation sites modulating gene expression) to new ones with greater freedom of decoding (i.e., a continuous cell phenotypic space). This leads to a new domain in code biology where biological systems are informatic attractors that navigate an energy metaspace through a complexity-noise balance, stalling in emergent niches where organic codes take meaning.
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Affiliation(s)
- Omar Paredes
- Computer Sciences Department, CUCEI, Universidad de Guadalajara, Mexico
| | | | - Adriana P Mendizabal
- Molecular Biology Laboratory, Farmacobiology Department, CUCEI, Universidad de Guadalajara, Mexico
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Markelova N, Glazunova O, Alikina O, Panyukov V, Shavkunov K, Ozoline O. Suppression of Escherichia coli Growth Dynamics via RNAs Secreted by Competing Bacteria. Front Mol Biosci 2021; 8:609979. [PMID: 33937321 PMCID: PMC8082180 DOI: 10.3389/fmolb.2021.609979] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 03/11/2021] [Indexed: 11/13/2022] Open
Abstract
With the discovery of secreted RNAs, it has become apparent that the biological role of regulatory oligonucleotides likely goes beyond the borders of individual cells. However, the mechanisms of their action are still comprehended only in general terms and mainly for eukaryotic microRNAs, which can interfere with mRNAs even in distant recipient cells. It has recently become clear that bacterial cells lacking interference systems can also respond to eukaryotic microRNAs that have targets in their genomes. However, the question of whether bacteria can perceive information transmitted by oligonucleotides secreted by other prokaryotes remained open. Here we evaluated the fraction of short RNAs secreted by Escherichia coli during individual and mixed growth with Rhodospirillum rubrum or Prevotella copri, and found that in the presence of other bacteria E. coli tends to excrete oligonucleotides homologous to alien genomes. Based on this observation, we selected four RNAs secreted by either R. rubrum or P. copri, together with one E. coli-specific oligonucleotide. Both fragments of R. rubrum 23S-RNA suppressed the growth of E. coli. Of the two fragments secreted by P. copri, one abolished the stimulatory effect of E. coli RNA derived from the 3'-UTR of ProA mRNA, while the other inhibited bacterial growth only in the double-stranded state with complementary RNA. The ability of two RNAs secreted by cohabiting bacteria to enter E. coli cells was demonstrated using confocal microscopy. Since selected E. coli-specific RNA also affected the growth of this bacterium, we conclude that bacterial RNAs can participate in inter- and intraspecies signaling.
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Affiliation(s)
- Natalia Markelova
- Laboratory of Functional Genomics and Cellular Stress, Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia
| | - Olga Glazunova
- Laboratory of Functional Genomics and Cellular Stress, Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia
| | - Olga Alikina
- Laboratory of Functional Genomics and Cellular Stress, Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia
| | - Valeriy Panyukov
- Department of Structural and Functional Genomics, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia.,Laboratory of Bioinformatics, Institute of Mathematical Problems of Biology, Pushchino, Russia
| | - Konstantin Shavkunov
- Laboratory of Functional Genomics and Cellular Stress, Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia.,Department of Structural and Functional Genomics, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia
| | - Olga Ozoline
- Laboratory of Functional Genomics and Cellular Stress, Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia.,Department of Structural and Functional Genomics, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia
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Chen KW, Chen JA. Functional Roles of Long Non-coding RNAs in Motor Neuron Development and Disease. J Biomed Sci 2020; 27:38. [PMID: 32093746 PMCID: PMC7041250 DOI: 10.1186/s12929-020-00628-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/12/2020] [Indexed: 12/14/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) have gained increasing attention as they exhibit highly tissue- and cell-type specific expression patterns. LncRNAs are highly expressed in the central nervous system and their roles in the brain have been studied intensively in recent years, but their roles in the spinal motor neurons (MNs) are largely unexplored. Spinal MN development is controlled by precise expression of a gene regulatory network mediated spatiotemporally by transcription factors, representing an elegant paradigm for deciphering the roles of lncRNAs during development. Moreover, many MN-related neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are associated with RNA metabolism, yet the link between MN-related diseases and lncRNAs remains obscure. In this review, we summarize lncRNAs known to be involved in MN development and disease, and discuss their potential future therapeutic applications.
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Affiliation(s)
- Kuan-Wei Chen
- Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
| | - Jun-An Chen
- Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
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Hussey MR, Burt A, Deyssenroth MA, Jackson BP, Hao K, Peng S, Chen J, Marsit CJ, Everson TM. Placental lncRNA expression associated with placental cadmium concentrations and birth weight. ENVIRONMENTAL EPIGENETICS 2020; 6:dvaa003. [PMID: 32411397 PMCID: PMC7211362 DOI: 10.1093/eep/dvaa003] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 01/01/2020] [Accepted: 02/03/2020] [Indexed: 05/22/2023]
Abstract
Heavy metal exposures, such as cadmium, can have negative effects on infant birth weight (BW)-among other developmental outcomes-with placental dysfunction potentially playing a role in these effects. In this study, we examined how differential placental expression of long non-coding RNAs (lncRNAs) may be associated with cadmium levels in placenta and whether differences in the expression of those lncRNAs were associated with fetal growth. In the Rhode Island Child Health Study, we used data from Illumina HiSeq whole transcriptome RNA sequencing (n = 199) to examine association between lncRNA expression and measures of infant BW as well as placental cadmium concentrations controlled for appropriate covariates. Of the 1191 lncRNAs sequenced, 46 demonstrated associations (q < 0.05) with BW in models controlling for infant sex, maternal age, BMI, maternal education, and smoking during pregnancy. Furthermore, four of these transcripts were associated with placental cadmium concentrations, with MIR22HG and ERVH48-1 demonstrating increases in expression associated with increasing cadmium exposure and elevated odds of small for gestational age birth, while AC114763.2 and LINC02595 demonstrated reduced expression associated with cadmium, but elevated odds of large for gestational age birth with increasing expression. We identified relationships between lncRNA expression with both placental cadmium concentrations and BW. This study provides evidence that disrupted placental expression of lncRNAs may be a part of cadmium's mechanisms of reproductive toxicity.
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Affiliation(s)
- Michael R Hussey
- Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, GA, USA
| | - Amber Burt
- Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, GA, USA
| | - Maya A Deyssenroth
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Brian P Jackson
- Department of Earth Sciences, Dartmouth College, Hanover, NH, USA
| | - Ke Hao
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shouneng Peng
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jia Chen
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Carmen J Marsit
- Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, GA, USA
| | - Todd M Everson
- Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, GA, USA
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Wang S, Mao C, Liu S. Peptides encoded by noncoding genes: challenges and perspectives. Signal Transduct Target Ther 2019; 4:57. [PMID: 31871775 PMCID: PMC6908703 DOI: 10.1038/s41392-019-0092-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/17/2019] [Accepted: 10/27/2019] [Indexed: 01/01/2023] Open
Abstract
In recent years, noncoding gene (NCG) translation events have been frequently discovered. The resultant peptides, as novel findings in the life sciences, perform unexpected functions of increasingly recognized importance in many fundamental biological and pathological processes. The emergence of these novel peptides, in turn, has advanced the field of genomics while indispensably aiding living organisms. The peptides from NCGs serve as important links between extracellular stimuli and intracellular adjustment mechanisms. These peptides are also important entry points for further exploration of the mysteries of life that may trigger a new round of revolutionary biotechnological discoveries. Insights into NCG-derived peptides will assist in understanding the secrets of life and the causes of diseases, and will also open up new paths to the treatment of diseases such as cancer. Here, a critical review is presented on the action modes and biological functions of the peptides encoded by NCGs. The challenges and future trends in searching for and studying NCG peptides are also critically discussed.
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Affiliation(s)
- Shuo Wang
- Changhai Hospital, Shanghai, 200433 China
| | - Chuanbin Mao
- Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, Institute for Biomedical Engineering, Science and Technology, University of Oklahoma, 101 Stephenson Parkway, Norman, OK 73019-5300 USA
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Zhao QJ, Zhang J, Xu L, Liu FF. Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma. World J Gastroenterol 2018; 24:3426-3439. [PMID: 30122881 PMCID: PMC6092581 DOI: 10.3748/wjg.v24.i30.3426] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 05/24/2018] [Accepted: 06/21/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To construct a long non-coding RNA (lncRNA) signature for predicting hepatocellular carcinoma (HCC) prognosis with high efficiency.
METHODS Differentially expressed lncRNAs (DELs) between HCC specimens and peritumor liver specimens were identified using the edgeR package to analyze The Cancer Genome Atlas (TCGA) LIHC dataset. Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival (OS) in a training set. These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model. Those lncRNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula. The prognostic value of this formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lncRNAs in the signature.
RESULTS Based on lncRNA expression profiling of 370 HCC patients from the TCGA database, we constructed a 5-lncRNA signature (AC015908.3, AC091057.3, TMCC1-AS1, DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis. HCC patients with high-risk scores based on the expression of the 5 lncRNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups. Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lncRNAs was independent of clinicopathological parameters. A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lncRNA signature showed improved prognostic power compared with the other two signatures. Functional enrichment analysis indicated that the 5 lncRNAs were potentially involved in metabolic processes, fibrinolysis and complement activation.
CONCLUSION Our present study constructed a 5-lncRNA signature that improves survival prediction and can be used as a prognostic biomarker for HCC patients.
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Affiliation(s)
- Qiu-Jie Zhao
- Department of Gastroenterology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Jiao Zhang
- Department of Gastroenterology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Lin Xu
- Department of Gastroenterology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Fang-Feng Liu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong Province, China
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