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The role of ncrna regulatory mechanisms in diseases-case on gestational diabetes

BRIEFINGS IN BIOINFORMATICS 2024年第1期25卷 bbad489页

作者： Gao, Dong Ren, Liping Hao, Yu-Duo Schaduangrat, Nalini Liu, Xiao-Wei Yuan, Shi-Shi Yang, Yu-He Wang, Yan Shoombuatong, Watshara Ding, Hui Univ Elect Sci & Technol China Ctr Informat Biol Chengdu Peoples R China Chengdu Neusoft Univ Chengdu Peoples R China Mahidol Univ Ctr Res Innovat & Biomed Informat Fac Med Technol Bangkok 10700 Thailand Beijing Hosp Dept Cardiovasc Med Beijing Peoples R China Chinese Acad Med Sci Beijing Hosp Inst Geriatr Med Natl Ctr Gerontol Beijing 100730 Peoples R China Univ Elect Sci & Technol China Ctr Informat Biol Sch Life Sci & Technol Chengdu 610054 Peoples R China

non-coding rnas (ncrnas) are a class of rna molecules that do not have the potential to encode proteins. Meanwhile, they can occupy a significant portion of the human genome and participate in gene expression regulation through various mechanisms. Gestational diabetes mellitus (GDM) is a pathologic condition of carbohydrate intolerance that begins or is first detected during pregnancy, making it one of the most common pregnancy complications. Although the exact pathogenesis of GDM remains unclear, several recent studies have shown that ncrnas play a crucial regulatory role in GDM. Herein, we present a comprehensive review on the multiple mechanisms of ncrnas in GDM along with their potential role as biomarkers. In addition, we investigate the contribution of deep learning-based models in discovering disease-specific ncrna biomarkers and elucidate the underlying mechanisms of ncrna. This might assist community-wide efforts to obtain insights into the regulatory mechanisms of ncrnas in disease and guide a novel approach for early diagnosis and treatment of disease.

关键词： non-coding rna gestational diabetes regulatory mechanism biomarkers attention mechanism

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Strategies to overcome chemoresistance in epithelial ovarian cancer: Navigating beyond challenges

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CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY 2025年 210卷 104706-104706页

作者： Nguyen, Que Thanh Thanh Kim, Jihye Yoo, Hee Chan Lee, Eun-Ju Chung Ang Univ Sch Med Dept Obstet & Gynecol 102 Heukseok Ro Seoul 156755 South Korea Chung Ang Univ Organoid Med Res Ctr Seoul 06974 South Korea Chung Ang Univ Coll Pharm Seoul 06974 South Korea

Epithelial ovarian cancer (EOC) is the most fetal gynecological malignancy. The main causes of treatment failure are primary and acquired chemoresistance that remains a major therapeutic challenge. The mechanisms underlying chemoresistance in EOC are complex and not fully understood. This review explores novel therapeutic strategies targeting chemoresistant EOC, including advanced drug delivery systems, targeting non-coding rnas, peptide-based therapies, immunotherapy, and the use of poly-ADP ribose polymerase inhibitors. By summarizing the latest research and potential treatments, this review aims to contribute to the development of more effective therapies for patients with chemoresistant EOC.

关键词： Chemoresistance Epithelial ovarian cancer Drug delivery systems non-coding rna Peptide Immunotherapy

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Lampbrush chromosomes of Danio rerio

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CHROMOSOME RESEARCH 2025年第1期33卷 1-19页

作者： Dedukh, D. Kulikova, T. Dobrovolskaia, M. Maslova, A. Krasikova, A. St Petersburg State Univ St Petersburg Russia Inst Anim Physiol & Genet Libechov Czech Republic

Danio rerio, commonly known as zebrafish, is an established model organism for the developmental and cell biology studies. Although significant progress has been made in the analysis of the D. rerio genome, cytogenetic studies face challenges due to the unclear identification of chromosomes. Here, we present a novel approach to the study of the D. rerio karyotype, focusing on the analysis of lampbrush chromosomes isolated from growing oocytes. Lampbrush chromosomes, existing during diplotene, serve as a powerful tool for high-resolution mapping and transcription analysis due to their profound decondensation and remarkable lateral loops decorated by rna polymerases and ribonucleoprotein (RNP) matrix. In D. rerio, lampbrush chromosomes are about 20 times longer than corresponding metaphase chromosomes. We found that the lampbrush chromosome stage karyotype of D. rerio is generally undifferentiated, except for several bivalents bearing distinct marker structures, including loops with complex RNP matrix and locus-associated nuclear bodies. Locus-associated nuclear bodies were enriched for coilin and snrnas;the loci where they formed presumably correspond to the histone gene clusters. Further, we observed the accumulation of splicing factors in giant terminal RNP aggregates on one bivalent. DAPI staining of Danio rerio lampbrush chromosomes revealed large and small chromomeres non-uniformly distributed along the axis. For example, D. rerio lampbrush chromosome 4, comprising the sex-determining region, is divided into two halves-with small chromomeres bearing long lateral loops and with large dense chromomeres bearing no or very tiny lateral loops. As centromeres were not distinguishable, we identified centromeric regions in all bivalents by FISH mapping of pericentromeric RFAL1, RFAL2, and RFAM tandem repeats. Through a combination of morphological analysis, immunostaining of marker structures, and centromere mapping, we developed cytological maps of D. rerio lampbrush c

关键词： Centromere FISH-mapping Germinal vesicle Histone locus bodies Karyotype analysis Lampbrush chromosomes non-coding rna Oocyte nucleus Tandem repeats Telomere Zebrafish

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Role of lncrna PVT1 in the progression of urological cancers: Novel insights into signaling pathways and clinical opportunities

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CELLULAR SIGNALLING 2025年 131卷 111736页

作者： Hashemi, Mehrdad Gholamrezaie, Hamidreza Ziyaei, Faezeh Asadi, Saba Naeini, Zahra Yousefian Salimian, Niloufar Enayat, Golnaz Sharifi, Nafiseh Aliahmadi, Melika Rezaie, Yasamin Soofi Khoushab, Saloomeh Rahimzadeh, Payman Miri, Hossein Abedi, Maryam Farahani, Najma Taheriazam, Afshin Nabavi, Noushin Entezari, Maliheh Islamic Azad Univ Farhikhtegan Hosp Tehran Med Sci Farhikhtegan Med Convergence Sci Res Ctr Tehran Iran Islamic Azad Univ Fac Adv Sci & Technol Tehran Med Sci Dept Genet Tehran Iran Islamic Azad Univ Fac Adv Sci & Technol Tehran Med Sci Dept Cellular & Mol Biol Tehran Iran Islamic Azad Univ Fac Basic Sci Dept Biol Shahrekord Branch Shahrekord Iran Univ Tehran Med Sci StudentsSci Res Ctr Surg Res Soc SRS Tehran Iran Islamic Azad Univ Fac Med Tehran Med Sci Branch Tehran Iran Univ Tehran Med Sci Canc Inst Dept Pathol Tehran Iran Islamic Azad Univ Tehran Med Sci Fac Med Dept Orthoped Tehran Iran

Urologic malignancies, encompassing cancers of the kidney, bladder, and prostate, represent approximately 25 % of all cancer cases. Recent advances have enhanced our understanding of PVT1's crucial functions. Long non- coding rnas influence both the onset and development of cancer, as well as epigenetic alterations. Recent findings have focused on PVT1's mechanism of action across several malignancies, particularly urologic cancers. Understanding the various functions of PVT1 linked to cancer is necessary for the development of cancer detection and treatment when PVT1 is dysregulated. Furthermore, recent advancements in genomic and epigenetic research have elucidated the complex regulatory networks that control PVT1 expression. Comprehending the intricate role of PVT1 Understanding the complex function of PVT1 in urologic cancers has substantial clinical implications. Here, we summarize some of the most recent findings about the carcinogenic effects of PVT1 signaling pathways and the possible treatment strategies for urological malignancies that target these pathways.

关键词： non-coding rna PVT1 Urological cancer Signaling pathway Lncrna

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Functional involvement of rnas and intrinsically disordered proteins in the assembly of heterochromatin

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BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 2025年第6期1869卷 130790页

作者： Obuse, Chikashi Nakayama, Jun-ichi Osaka Univ Grad Sch Sci Osaka 5600043 Japan Natl Inst Basic Biol Div Chromatin Regulat Okazaki 4448585 Japan SOKENDAI Grad Inst Adv Studies Basic Biol Program Okazaki 4448585 Japan

Heterochromatin is a highly condensed chromatin structure observed in the nuclei of eukaryotic cells. It plays a pivotal role in repressing undesired gene expression and establishing functional chromosomal domains, including centromeres and telomeres. Heterochromatin is characterized by specific histone modifications and the formation of higher-order chromatin structures mediated by proteins, such as HP1 and Polycomb repressive complexes (PRCs), which recognize the specific histone modifications. Recent studies have identified the involvement of non-coding rnas (ncrnas) and intrinsically disordered proteins (IDPs) in heterochromatin, leading to the proposal of a new model in which liquid-liquid phase separation (LLPS) contributes to heterochromatin formation and function. This emerging model not only broadens our understanding of heterochromatin's molecular mechanisms but also provides insights into its dynamic regulation depending on cellular context. Such advancements pave the way for exploring heterochromatin's role in genome organization and stability, as well as its implications in development and disease.

关键词： Heterochromatin Liquid-liquid phase separation non-coding rna Intrinsically disordered protein Histone modification

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In silico analysis of lncrna-mirna-mrna signatures related to Sorafenib effectiveness in liver cancer cells

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World Journal of Gastroenterology 2025年第3期31卷 84-102页

作者： Patricia de la Cruz-Ojeda Ester Parras-Martínez Raquel Rey-Pérez Jordi Muntané Functional Genomics of Solid Tumors Laboratory Centre de Recherche des CordeliersParis 75006France Department of Oncology Surgery Cell Therapy and Organ TransplantationInstitute of Biomedicine of SevilleVirgen del Rocio University HospitalSeville 41013Spain Biomedical Research Center for Hepatic and Digestive Diseases CIBERehdMadrid 28029Spain Department of Medical Physiology and Biophysics University of SevilleSeville 41009Spain

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology *** is still a recommended treatment for a large proportion of patients with advanced *** patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 *** To define the long non-codingrna-microrna-mrna(lncrna-mirna-mrna)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in rnaseq studies using Sorafenib-treated HepG2 and SNU449 *** available software analyses allowed us to establish the lncrna-mirna-mrna regulatory axes following treatment in HepG2 and SNU449 *** HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 *** rna,including small and long rna,was extracted with a commercial miRNeasy *** was carried out for the identification of changes in lncrna-mirna-mrna regulatory *** MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 ***12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 *** axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib *** Critical lncrnas acting as sponges of mirna were identified that regulated mrna expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关键词： Cell culture Hepatocellular carcinoma non-coding rna rnaseq Sorafenib

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Glutamine missense suppressor transfer rnas inhibit polyglutamine aggregation

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MOLECULAR THERAPY NUCLEIC ACIDS 2025年第1期36卷 102442页

作者： Tennakoon, Rasangi Bily, Teija M. I. Hasan, Farah Syal, Sunidhi Voigt, Aaron Balci, Tugce B. Hoffman, Kyle S. O'Donoghue, Patrick Univ Western Ontario Dept Biochem London ON N6A 5C1 Canada Rhein Westfal TH Aachen Dept Neurol D-52062 Aachen Germany Univ Western Ontario Dept Paediat London ON N6A 5C1 Canada Bioinformat Solut Inc Waterloo ON N2L 3K8 Canada Univ Western Ontario Dept Chem London ON N6A 5C1 Canada

Huntington's disease (HD) is caused by polyglutamine (polyQ) repeat expansions in the huntingtin gene. HD-causative polyQ alleles lead to protein aggregation, which is a prerequisite for disease. Translation fidelity modifies protein aggregation, and several studies suggest that mutating one or two glutamine (Gln) residues in polyQ reduces aggregation. Thus, we hypothesized that missense suppression of Gln codons with other amino acids will reduce polyQ aggregate formation in cells. In neuroblastoma cells, we assessed trna variants that misread Gln codons with serine (trnaSerC/UUG) or alanine (trnaAlaC/UUG). The trnas with the CUG anticodon were more effective at suppressing the CAG repeats in polyQ, and serine and alanine mis-incorporation had differential impacts on polyQ. The expression of trnaSerCUG reduced polyQ protein production as well as both soluble and insoluble aggregate formation. In contrast, cells expressing trnaAlaCUG selectively decreased insoluble polyQ aggregate formation by 2-fold. Mass spectrometry confirmed Ala mis-incorporation at an average level of X20% per Gln codon. Cells expressing the missense suppressor trnas showed no cytotoxic effects and no defects in growth or global protein synthesis levels. Our findings demonstrate that trna-dependent missense suppression of Gln codons is well tolerated in mammalian cells and significantly reduces polyQ levels and aggregates that cause HD.

关键词： MT: non-coding rnas Huntington's disease HD gene therapy mistranslation missense suppression non-coding rna polyglutamine polyQ protein aggregation trna therapeutics

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circHIPK2 promotes malignant progression of laryngeal squamous cell carcinoma through the miR-889-3p/MCTS1/IL-6 axis

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TRANSLATIONAL ONCOLOGY 2025年 56卷 102390-102390页

作者： Sun, Yang-Guang Yu, Zhen-Kun Chen, Xi Zhang, Si-Yao Wu, Wan-Juan Liu, Kai Cheng, Lei Nanjing Med Univ Affiliated Hosp 1 Dept Otorhinolaryngol Nanjing 210029 Peoples R China Nanjing Med Univ BenQ Med Ctr Dept Otolaryngol Head & Neck Surg Nanjing Med Key Lab Laryngopharynx Head & Neck Onc Nanjing 210019 Peoples R China Nanjing Med Univ Affiliated Hosp 1 Dept Allergol Nanjing 210029 Peoples R China

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck with a poor prognosis. The role of circrnas in LSCC remains largely unknown. In this study, quantitative real-time PCR (qRTPCR), Sanger sequencing and fluorescence in situ hybridization were undertaken to detect the expression, localization, and clinical significance of circHIPK2 in LSCC tissues and TU686 and TU212 cells. The functions of circHIPK2 in LSCC were explored through proliferation analysis, EdU staining, colony formation assay, wound healing assay, and Transwell assay. The regulatory mechanisms underpinning circHIPK2, miR-889-3p, and MCTS1 were investigated using luciferase assay, Western blotting, and qRT-PCR. We found that LSCC tissues and cells demonstrated high expression of circHIPK2 that was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circHIPK2 inhibited the proliferation and migration of LSCC cells in vitro. Mechanistic studies showed that circHIPK2 competitively bound to miR-889-3p, elevated MCTS1 level, promoted IL-6 secretion, and ultimately accelerated the malignant progression of LSCC. In conclusion, an axis involving circHIPK2, miR-889-3p, MCTS1 and IL-6 regulates the malignant progression of LSCC. circHIPK2 expression may serve as a novel diagnostic and prognostic biomarker for LSCC.

关键词： Laryngeal squamous cell carcinoma non-coding rna circHIPK2 miR-889-3p MCTS1 IL-6 Tumor microenvironment

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Targeting micrornas as a promising anti-cancer therapeutic strategy against traffic-related air pollution-mediated lung cancer

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CANCER AND METASTASIS REVIEWS 2024年第3期43卷 1117-1117页

作者： Panahi, Hamed Kazemi Shariat Dehhaghi, Mona Guillemin, Gilles J. Peng, Wanxi Aghbashlo, Mortaza Tabatabaei, Meisam Henan Agr Univ Henan Prov Engn Res Ctr Biomass Value Added Prod Sch Forestry Zhengzhou 450002 Peoples R China Macquarie Univ Fac Med Hlth & Human Sci Dept Biomed Sci Neuroinflammat Grp Sydney NSW Australia Biofuel Res Team BRTeam Kuala Terengganu Terengganu Malaysia ICTRYM Pty Ltd Sydney Australia Univ Tehran Coll Agr & Nat Resources Fac Agr Engn & Technol Dept Mech Engn Agr Machinery Karaj Iran Univ Malaysia Terengganu Higher Inst Ctr Excellence HICoE Inst Trop Aquaculture & Fisheries AKUATROP Kuala Nerus 21030 Terengganu Malaysia Saveetha Inst Med & Tech Sci Saveetha Dent Coll Dept Biomat Chennai 600077 India

Air pollutants are increasingly emitted into the atmosphere because of the high dependency of humans on fossil-derived fuels. Wind speed and direction assisted high dispersibility and uncontrolled nature of air pollution across geo-/demographical borders, making it one of the major global concerns. Besides climate change, air pollution has been found to be associated with various diseases, such as cancer. Lung cancer, which is the world’s most common type of cancer, has been found to be associated with traffic-related air pollution. Research and political efforts have been taken to explore green/renewable energy sources. However, these efforts at the current intensity cannot cope with the increasing need for fossil fuels. More specifically, political tensions such as the Russian-Ukraine war, economic tension (e.g., China-USA economic tensions), and other issues (e.g., pandemic, higher inflation rate, and poverty) significantly hindered phasing out fossil fuels. In this context, an increasing global population will be exposed to traffic-related air pollution, which justifies the current uptrend in the number of lung cancer patients. To combat this health burden, novel treatments with higher efficiency and specificity must be designed. One of the potential “life changer” options is microrna (mirna)-based therapy to target the expression of oncogenic genes. That said, this review discusses the association of traffic-related air pollution with lung cancer, the changes in indigenous mirnas in the body during lung cancer, and the current status of mirna therapeutics for lung cancer treatment. We believe that the article will significantly appeal to a broad readership of oncologists, environmentalists, and those who work in the field of (bio)energy. It may also gain the policymakers’ attention to establish better health policies and regulations about air pollution, for example, by promoting (bio)fuel exploration, production, and consumption.

关键词： Lung cancer Microrna Nitrogen oxides non-coding rna Particulate matter Treatment

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non-coding rnas, metabolic stress and adaptive mechanisms in cancer

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CANCER LETTERS 2020年 491卷 60-69页

作者： Liu, Xiaoying Feng, Shanshan Zhang, Xu Dong Li, Jinming Zhang, Kaiguang Wu, Mian Thorne, Rick F. Zhengzhou Univ Translat Res Inst Henan Prov Peoples Hosp Zhengzhou 450053 Henan Peoples R China Zhengzhou Univ Acad Med Sci Peoples Hosp Mol Pathol Ctr Zhengzhou 450053 Henan Peoples R China Anhui Med Univ Sch Life Sci Hefei 230032 Peoples R China Jinan Univ Sch Life Sci & Technol Dept Dev & Regenerat Biol Minist EducKey Lab Regenerat Med Guangzhou Peoples R China Univ Newcastle Sch Biomed Sci & Pharm Newcastle NSW Australia Univ Sci & Technol China Affiliated Hosp 1 Hefei 230027 Peoples R China Henan Univ Sch Clin Med Key Lab Stem Cell Differentiat & Modificat Zhengzhou Peoples R China Univ Newcastle Sch Environm & Life Sci Newcastle NSW Australia

Metabolic reprogramming in cancer describes the multifaceted alterations in metabolism that contribute to tumorigenesis. Major determinants of metabolic phenotypes are the changes in signalling pathways associated with oncogenic activation together with cues from the tumor microenvironment. Therein, depleted oxygen and nutrient levels elicit metabolic stress, requiring cancer cells to engage adaptive mechanisms. non-coding rnas (ncrnas) act as regulatory elements within metabolic pathways and their widespread dysregulation in cancer contributes to altered metabolic phenotypes. Indeed, ncrnas are the regulatory accomplices of many prominent effectors of metabolic reprogramming including c-MYC and HIFs that are activated by metabolic stress. By example, this review illustrates the range of ncrnas mechanisms impacting these effectors throughout their DNA-rna-protein lifecycle along with presenting the mechanistic roles of ncrnas in adaptive responses to glucose, glutamine and lipid deprivation. We also discuss the facultative activation of metabolic enzymes by ncrnas, a phenomenon which may reflect a broad but currently invisible level of metabolic regulation. Finally, the translational challenges associated with ncrna discoveries are discussed, emphasizing the gaps in knowledge together with importance of understanding the molecular basis of ncrna regulatory mechanisms.

关键词： c-MYC HIF1alpha Metabolic reprogramming Metabolic stress non-coding rna Tumor microenvironment

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