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Mitochondrial DNA. Part B, Resources 2023The complete chloroplast genome sequence of (Bosch) Copel. was determined in the present study. The genome is 145,943 base pairs (bp) in length and comprised two...
The complete chloroplast genome sequence of (Bosch) Copel. was determined in the present study. The genome is 145,943 base pairs (bp) in length and comprised two inverted repeats (32,990 bp) between a large single copy (92,170 bp) and a small single copy (20,783 bp). It contains 88 coding genes, 8 rRNA genes, 34 tRNA genes, and 1 pseudogene of and the GC content is 37.6%. Molecular phylogenetic analysis based on the plastid genome sequences of related taxa strongly supported the monophyly of the family Hymenophyllaceae, and the genus was a sister group of . In addition, compared to two large deletions of 453 bp and 878 bp were found in the IGS regions of and rrn16-trnV-GAC of cp genome, respectively.
PubMed: 37521905
DOI: 10.1080/23802359.2023.2238936 -
Nucleic Acids Research Mar 2024Much insight has been gained on how stem cells maintain genomic integrity, but less attention has been paid to how they maintain their transcriptome. Here, we report...
Much insight has been gained on how stem cells maintain genomic integrity, but less attention has been paid to how they maintain their transcriptome. Here, we report that the PIWI protein SMEDWI-1 plays a role in the filtering of dysfunctional transcripts from the transcriptome of planarian stem cells. SMEDWI-1 accomplishes this through association with the ribosomes during the pioneer round of translation, and processing of poorly translated transcripts into piRNAs. This results in the removal of such transcripts from the cytoplasmic pool and at the same time creates a dynamic pool of small RNAs for post-transcriptional surveillance through the piRNA pathway. Loss of SMEDWI-1 results in elevated levels of several non-coding transcripts, including rRNAs, snRNAs and pseudogene mRNAs, while reducing levels of several coding transcripts. In the absence of SMEDWI-1, stem cell colonies are delayed in their expansion and a higher fraction of descendants exit the stem cell state, indicating that this transcriptomic sanitation mediated by SMEDWI-1 is essential to maintain stem cell health. This study presents a new model for the function of PIWI proteins in stem cell maintenance, that complements their role in transposon repression, and proposes a new biogenesis pathway for piRNAs in stem cells.
Topics: Argonaute Proteins; DNA Transposable Elements; Helminth Proteins; Piwi-Interacting RNA; Platyhelminths; Proteins; RNA Interference; RNA, Small Interfering; Stem Cells; Animals
PubMed: 38142432
DOI: 10.1093/nar/gkad1212 -
BMC Medical Genomics Aug 2023To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2...
OBJECTIVE
To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2 and depths of various immune cell infiltration depths. The relationship between different immune checkpoints were also analyzed.
METHODS
First, the expression of EZH2 in pan-cancer (18 malignancies) was analyzed with the TCGA database. Hepatocellular carcinoma (HCC) tissues of 374 cases and normal tissues of 50 cases were analyzed in terms of the differential expression, overall survival (OS) and progression-free-survival (PFS). Then, we conducted GO and KEGG enrichment analysis on target gene. We also analyzed mRNA-miRNA and MicroRNA (miRNA)- long non-coding RNA (lncRNA) correlation with starbase databse, so as to determine the potential ceRNA mechanism associated with EZH2. Finally, immunoassay and drug-sensitivity analysis of EZH2 was performed.
RESULTS
Seven potential EZH2-related ceRNA pathways were screened out, namely lncRNA: Small Nucleolar RNA Host Gene 1 (SNHG1), SNHG 3, and SNHG 6-miR-101-3p-EZH2; and lncRNA: Long Intergenic Non-Protein Coding RNA 1978 (LINC01978), SNHG12, Ring Finger Protein 216 Pseudogene 1 (RNF216P1), and Coiled-coil Domain Containing 18 Antisense RNA 1 (CCDC18-AS1)-let-7c-5p-EZH2. Finally, 4 potential EZH2-related ceRNA pathways were identified through qPCR.According to immune correlation analysis, EZH2 may be positively correlated with T cells follicular helper, T cells Cluster of differentiation (CD)4 memory activated, Macrophages M0, and B cells memory (P < 0.05, cof > 0.2); while be negatively correlated with T cells CD4 + memory resting (P < 0.05, cof < -0.2). And EZH2 is positively correlated with Programmed Cell Death 1 (PDCD1) (R = 0.22), CD274 (R = 0.3) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (R = 0.23). According to drug sensitivity analysis, patients in the high expression group were more susceptible to the effects of various drugs including Sorafenib, 5-Fluorouracil, Doxorubicin, Etoposide, Paclitaxel, and Vinorelbine than those with low expression.
CONCLUSION
This study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p-EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Enhancer of Zeste Homolog 2 Protein; RNA, Long Noncoding; Liver Neoplasms; MicroRNAs; Immunoassay
PubMed: 37626362
DOI: 10.1186/s12920-023-01594-9 -
Proceedings of the National Academy of... May 2024Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated...
Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated glycolysis, yet effective strategies targeting cancer cell metabolic reprogramming to overcome therapeutic resistance in ovarian cancer remain elusive. Here, we revealed that epigenetic silencing of Otubain 2 () is a driving force for mitochondrial metabolic reprogramming in ovarian cancer, which promotes tumorigenesis and chemoresistance. Mechanistically, OTUB2 silencing destabilizes sorting nexin 29 pseudogene 2 (SNX29P2), which subsequently prevents hypoxia-inducible factor-1 alpha (HIF-1α) from von Hippel-Lindau tumor suppressor-mediated degradation. Elevated HIF-1α activates the transcription of carbonic anhydrase 9 () and drives ovarian cancer progression and chemoresistance by promoting glycolysis. Importantly, pharmacological inhibition of CA9 substantially suppressed tumor growth and synergized with carboplatin in the treatment of -silenced ovarian cancer. Thus, our study highlights the pivotal role of OTUB2/SNX29P2 in suppressing ovarian cancer development and proposes that targeting CA9-mediated glycolysis is an encouraging strategy for the treatment of ovarian cancer.
Topics: Female; Ovarian Neoplasms; Humans; Mitochondria; Carbonic Anhydrase IX; Cell Line, Tumor; Animals; Mice; Antigens, Neoplasm; Hypoxia-Inducible Factor 1, alpha Subunit; Glycolysis; Gene Silencing; Gene Expression Regulation, Neoplastic; Drug Resistance, Neoplasm; Metabolic Reprogramming
PubMed: 38701117
DOI: 10.1073/pnas.2315348121 -
Current Molecular Medicine 2024Cancer is a persistent and urgent health problem that affects the entire world. Not long ago, regulatory biomolecules referred to as long noncoding RNAs (lncRNAs) might... (Review)
Review
Cancer is a persistent and urgent health problem that affects the entire world. Not long ago, regulatory biomolecules referred to as long noncoding RNAs (lncRNAs) might have value for their innate abundance and stability. These single-stranded RNAs potentially interfere with several physiological and biochemical cellular processes involved in many human pathological situations, particularly cancer diseases. Ferritin heavy chain1 pseudogene 3 (FTH1P3), a lncRNA that is ubiquitously transcribed and belongs to the ferritin heavy chain (FHC) family, represents a novel class of lncRNAs primarily found in oral squamous cell carcinoma. Further research has shown that FTH1P3 is involved in other malignancies such as uveal melanoma, glioma, esophageal squamous cell carcinoma, non-small cell lung cancer, breast cancer, laryngeal squamous cell carcinoma, and cervical cancer. Accordingly, FTH1P3 significantly enhances cancer symptoms, including cell proliferation, invasion, metastasis, chemoresistance, and inhibition of apoptosis through many specific mechanisms. Notably, the clinical data significantly demonstrated the association of FTH1P3 overexpression with poor prognosis and poor overall survival within the examined samples. Here, we summarize all the research published to date (13 articles) on FTH1P3, focusing on the biological function underlying the regulatory mechanism and its possible clinical relevance.
Topics: Humans; RNA, Long Noncoding; Neoplasms; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Prognosis; Animals
PubMed: 37491858
DOI: 10.2174/1566524023666230724141353 -
Clinical and Experimental Medicine Jan 2024Colorectal cancer (CRC) and gastric cancer (GC) are major contributors to cancer-related mortality worldwide. Despite advancements in understanding molecular mechanisms... (Review)
Review
Colorectal cancer (CRC) and gastric cancer (GC) are major contributors to cancer-related mortality worldwide. Despite advancements in understanding molecular mechanisms and improved drug treatments, the overall survival rate for patients remains unsatisfactory. Metastasis and drug resistance are major challenges contributing to the high mortality rate in both CRC and GC. Recent research has shed light on the role of long noncoding RNAs (lncRNAs) in the development and progression of these cancers. LncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions with microRNAs (miRNAs) and proteins. They can serve as miRNA precursors or pseudogenes, modulating gene expression at transcriptional and post-transcriptional levels. Additionally, circulating lncRNAs have emerged as non-invasive biomarkers for the diagnosis, prognosis, and prediction of drug therapy response in CRC and GC. This review explores the intricate relationship between lncRNAs and CRC/GC, encompassing their roles in cancer development, progression, and chemoresistance. Furthermore, it discusses the potential of lncRNAs as therapeutic targets in these malignancies. The interplay between lncRNAs, miRNAs, and tumor microenvironment is also highlighted, emphasizing their impact on the complexity of cancer biology. Understanding the regulatory landscape and molecular mechanisms governed by lncRNAs in CRC and GC is crucial for the development of effective diagnostic and prognostic biomarkers, as well as novel therapeutic strategies. This review provides a comprehensive overview of the current knowledge and paves the way for further exploration of lncRNAs as key players in the management of CRC and GC.
Topics: Humans; RNA, Long Noncoding; Prognosis; Stomach Neoplasms; MicroRNAs; Colorectal Neoplasms; Tumor Microenvironment
PubMed: 38294554
DOI: 10.1007/s10238-023-01260-5 -
BMC Biology Nov 2023Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth....
BACKGROUND
Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth. Particularly, de novo gene birth is a widespread process, and many examples continue to be discovered across diverse evolutionary lineages. However, the general mechanisms that lead to functionalization are poorly understood, and estimated rates of de novo gene birth remain contentious. Here, we address this problem within a model that takes into account mutations and structural variation, allowing us to estimate the likelihood of emergence of new functions at non-functional loci.
RESULTS
Assuming biologically reasonable mutation rates and mutational effects, we find that functionalization of non-genic loci requires the realization of strict conditions. This is in line with the observation that most de novo genes are localized to the vicinity of established genes. Our model also provides an explanation for the empirical observation that emerging proto-genes are often lost despite showing signs of adaptation.
CONCLUSIONS
Our work elucidates the properties of non-genic loci that make them fertile for adaptation, and our results offer mechanistic insights into the process of de novo gene birth.
Topics: Evolution, Molecular; Mutation; Biological Evolution
PubMed: 37957718
DOI: 10.1186/s12915-023-01745-5 -
Genes, Chromosomes & Cancer Jan 2024PMS2 germline pathogenic variants are one of the major causes for Lynch syndrome and constitutional mismatch repair deficiencies. Variant identification in the 3' region...
PMS2 germline pathogenic variants are one of the major causes for Lynch syndrome and constitutional mismatch repair deficiencies. Variant identification in the 3' region of this gene is complicated by the presence of the pseudogene PMS2CL which shares a high sequence homology with PMS2. Consequently, short-fragment screening strategies (NGS, Sanger) may fail to discriminate variant's gene localization. Using a comprehensive analysis strategy, we assessed 42 NGS-detected variants in 76 patients and found 32 localized on PMS2 while 6 on PMS2CL. Interestingly, four variants were detected in either of them in different patients. Clinical phenotype was well correlated to genotype, making it very helpful in variant assessment. Our findings emphasize the necessity of more specific complementary analyses to confirm the gene origin of each variant detected in different individuals in order to avoid variant misinterpretation. In addition, we characterized two PMS2 genomic alterations involving Alu-mediated tandem duplication and gene conversion. Those mechanisms seemed to be particularly favored in PMS2 which contribute to frequent genomic rearrangements in the 3' region of the gene.
Topics: Humans; Mismatch Repair Endonuclease PMS2; Colorectal Neoplasms; Pseudogenes; Colorectal Neoplasms, Hereditary Nonpolyposis; Germ-Line Mutation
PubMed: 37534630
DOI: 10.1002/gcc.23193 -
The New Phytologist Jul 2023Gluten is composed of glutenins and gliadins and determines the viscoelastic properties of dough and end-use quality in wheat (Triticum aestivum L.). Gliadins are...
Gluten is composed of glutenins and gliadins and determines the viscoelastic properties of dough and end-use quality in wheat (Triticum aestivum L.). Gliadins are important for wheat end-use traits, but the contribution of individual gliadin genes is unclear, since gliadins are encoded by a complex, multigenic family, including many pseudogenes. We used CRISPR/Cas9-mediated gene editing and map-based cloning to investigate the contribution of the γ-gliadin genes annotated in the wheat cultivar 'Fielder', showing that Gli-γ1-1D and Gli-γ2-1B account for most of the γ-gliadin accumulation. The impaired activity of only two γ-gliadin genes in knockout mutants improved end-use quality and reduced gluten epitopes associated with celiac disease (CD). Furthermore, we identified an elite haplotype of Gli-γ1-1D linked to higher end-use quality in a wheat germplasm collection and developed a molecular marker for this allele for marker-assisted selection. Our findings provide information and tools for biotechnology-based and classical breeding programs aimed at improving wheat end-use quality.
Topics: Gliadin; Triticum; Alleles; Plant Breeding; Glutens
PubMed: 36617723
DOI: 10.1111/nph.18722 -
Pathology, Research and Practice Aug 2023Due to their high prevalence, gastrointestinal cancers are one of the key causes of cancer-related death globally. The development of drug-resistant cancer cell... (Review)
Review
Due to their high prevalence, gastrointestinal cancers are one of the key causes of cancer-related death globally. The development of drug-resistant cancer cell populations is a major factor in the high mortality rate, and it affects about half of all cancer patients. Because of advances in our understanding of cancer molecular biology, non-coding RNAs (ncRNAs) have emerged as critical factors in the initiation and development of gastrointestinal cancers. Gene expression can be controlled in several ways by ncRNAs, including through epigenetic changes, interactions between microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and proteins, and the function of lncRNAs as miRNA precursors or pseudogenes. As lncRNAs may be detected in the blood, circulating ncRNAs have emerged as a promising new class of non-invasive cancer biomarkers for use in the detection, staging, and prognosis of gastrointestinal cancers, as well as in the prediction of therapy efficacy. In this review, we assessed the role lncRNAs play in the progression, and maintenance of colorectal cancer, and how they might be used as therapeutic targets in the future.
Topics: Humans; RNA, Long Noncoding; MicroRNAs; RNA, Untranslated; Gastrointestinal Neoplasms; Epigenesis, Genetic
PubMed: 37467635
DOI: 10.1016/j.prp.2023.154680