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non-coding rna in cartilage regeneration: regulatory mechanism and therapeutic strategies

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 2025年 13卷 1522303页

作者： Wen, Mengnan Guo, Xueqiang Zhang, Jingdi Li, Yunian Li, Jixiang Fan, Zhenlin Ren, Wenjie Xinxiang Med Univ Affiliated Hosp 3 Inst Hlth Cent Plain Clin Med Ctr Tissue Engn & Regenerat Xinxiang Peoples R China Xinxiang Med Univ Sch Basic Med Sci Henan Key Lab Med Tissue Regenerat Xinxiang Peoples R China Xinxiang Med Univ Junji Coll Xinxiang Peoples R China

The pathogenesis of cartilage injury and degeneration is exceptionally complex. In addition to being associated with osteoarthritis and trauma, factors such as age, gender, obesity, inflammation, and apoptosis of chondrocytes are also considered significant influencing factors. Due to the lack of direct blood supply, lymphatic circulation, and neural innervation, coupled with low metabolic activity, the self-repair capability of cartilage after injury is extremely limited, making its treatment quite challenging. Recent research indicated that ncrna, a class of rna transcribed from the genome that does not encode proteins, played a crucial regulatory role in various disease processes. Particularly noteworthy is its positive regulatory role in cartilage regeneration, achieved through the modulation of the inflammatory microenvironment, promotion of chondrocyte proliferation, inhibition of chondrocyte degradation, and facilitation of the recruitment and differentiation of bone marrow mesenchymal stem cells into chondrocytes. In the earlier phase, we conducted a review and outlook on therapeutic strategies for the regeneration of articular cartilage injuries. This article specifically focuses on summarizing the regulatory roles and research advancements of ncrna in cartilage regeneration, as well as its contributions to the clinical application of gene therapy for cartilage defects.

关键词： cartilage regeneration non-coding rna gene therapy tissue engineering and regenerative medicine OA

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non-coding rna as a key regulator and novel target of apoptosis in diabetic cardiomyopathy: Current status and future prospects

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CELLULAR SIGNALLING 2025年 128卷 111632页

作者： Liu, Yicheng Yuan, Jie Zhang, Yuhang Ma, Ting Ji, Qianqian Tian, Sheng Liu, Chunxiao Shandong Univ Tradit Chinese Med Coll Rehabil Med Jinan 250355 Peoples R China Shandong Univ Tradit Chinese Med Affiliated Hosp Sci & Technol Dept Jinan 250014 Peoples R China Taian Hosp Tradit Chinese Med Dept One Cardiovasc Dis Tai An 271000 Peoples R China Shandong Univ Qilu Hosp Dept Cardiovasc Surg Jinan 250012 Peoples R China Macau Univ Sci & Technol Fac Chinese Med Taipa 999078 Macao Peoples R China Macau Univ Sci & Technol State Key Lab Qual Res Chinese Med Taipa 999078 Macao Peoples R China Shandong Univ Tradit Chinese Med Innovat Inst Chinese Med & Pharm Jinan 250355 Peoples R China

The occurrence of diabetic cardiomyopathy (DCM) can be independent of several risk factors such as hypertension and myocardial ischemia, which can lead to heart failure, thus seriously threatening human health and life. Sustained hyperglycemic stimulation can induce cardiomyocyte apoptosis, which is recognized as the pathological basis of DCM. It has been demonstrated that dysregulation induced by apoptosis is closely associated to progression of DCM, but mechanisms behind it requires further clarification. Currently, increasing evidence has shown that non-coding rna (ncrna), especially microrna, long-chain non-coding rna (lncrna), and circular rna (circrna), play a regulative role in apoptosis, thus affecting the progression of DCM. Notably, some ncrnas have also exhibit potential significance as biomarkers and/or therapeutic targets for patients with DCM. In this review, recent findings regarding the potential mechanisms of ncrna in regulating apoptosis and their role in the progression of DCM were systematically summarized in this research. The conclusion reveals that ncrna abnormalities exert a crucial role in pathological changes of DCM, which offers potential therapeutic targets for the prevention of DCM.

关键词： non-coding rna Diabetic cardiomyopathy Cell apoptosis Oxidative stress Endoplasmic reticulum stress Signal transduction Signal regulation

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non-coding rna RMRP governs RAB31-dependent MMP secretion, enhancing ovarian cancer invasion

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 2025年第5期1871卷 167781页

作者： Lee, Ki Jun Ahn, Ji-Hye Kim, Jin-Hyung Lee, Yong Sun Lee, Ju-Seog Lee, Jae-Hyung Kim, Tae Jin Choi, Jung-Hye Kyung Hee Univ Dept Biomed & Pharmaceut Sci Seoul South Korea Kyung Hee Univ Coll Pharm Seoul South Korea Woosuk Univ Coll Pharm Dept Korean Pharm Wanju South Korea Natl Canc Ctr Grad Sch Canc Sci & Policy Dept Canc Biomed Sci Goyang South Korea Univ Texas MD Anderson Canc Ctr Dept Syst Biol Houston TX USA Kyung Hee Univ Coll Dent Dept Oral Microbiol Seoul South Korea Konkuk Univ Sch Med Dept Obstet & Gynecol Seoul South Korea

non-coding rnas (ncrnas) are frequently dysregulated in various cancers and have been implicated in the etiology and progression of cancer. Ovarian cancer, the most fatal gynecological cancer, has a poor prognosis and a high patient fatality rate due to metastases. In this study, we classified patients with ovarian cancer into three groups based on their ncrna expression levels. Notably, an ncrna transcribed by rna polymerase III, rna component of mitochondrial rna processing endoribonuclease (RMRP), is highly expressed in a group with a poor prognosis. Functional assays using SKOV3 and HeyA8 human ovarian cancer cell lines revealed that while RMRP modulation had no significant effect on cell viability, it markedly enhanced cell invasion. Knockdown and ectopic expression experiments demonstrated that RMRP promotes the secretion of matrix metalloproteinase (MMP)-2 and -9, thereby facilitating ovarian cancer cell invasiveness. Transcriptomic analysis further revealed a positive correlation between RMRP expression and genes involved in cellular localization, including RAB31, a member of the Ras-related protein family. Notably, RAB31 knockdown abrogated the pro-invasive effects of RMRP, identifying it as a key downstream effector in SKOV3 and HeyA8 cells. In addition, Mechrna analysis identified RAB31 as a putative RMRP-interacting transcript. These findings establish RMRP as a critical regulator of RAB31-dependent MMP secretion and ovarian cancer cell invasion. Moreover, our results suggest that RMRP could serve as a promising prognostic biomarker for ovarian cancer.

关键词： Ovarian cancer RMRP RAB31 Matrix metalloproteinases non-coding rna Cell invasion

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non-coding rna-mediated granulosa cell dysfunction during ovarian aging: From mechanisms to potential interventions

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non-coding rna RESEARCH 2025年 12卷 102-115页

作者： Dong, Li Wu, Haicui Qi, Fanghua Xu, Yuan Chen, Wen Wang, Yuqi Cai, Pingping Shandong Univ Tradit Chinese Med Sch Clin Med 1 Jinan Peoples R China Shandong Univ Tradit Chinese Med Affiliated Hosp Dept Reprod & Genet Jinan Peoples R China Shandong First Med Univ Shandong Prov Hosp Dept Tradit Chinese Med Jinan 250021 Peoples R China

As the earliest aging organ in the reproductive system, the ovary has both reproductive and endocrine functions, which are closely related to overall female health. The exact pathogenesis of ovarian aging (OA) remains incompletely understood, with granulosa cells (GCs) dysfunction playing a significant role in this process. Recent advancements in research and biotechnology have highlighted the importance of non-coding rnas (ncrnas), including micro rnas, long non-coding rnas, and circular rnas, in regulating the biological functions of GCs through gene expression modulation. This paper provides a comprehensive overview of the role of ncrnas in various cellular functions such as apoptosis, autophagy, proliferation, and steroid synthesis in GCs, and explores the underlying regulatory mechanisms. Additionally, the therapeutic potential of ncrnas, particularly those carried by exosomes derived from mesenchymal stem cells, in delaying OA is discussed. Understanding the regulatory mechanisms of ncrnas in GC function and the current progress in this field is crucial for identifying effective biomarkers and therapeutic targets, ultimately aiding in the early diagnosis, prognostic assessment, and individualized treatment of OA.

关键词： non-coding rna Ovarian aging Granulosa cell Biological function Exosome

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Theoretical perspectives and clinical applications of non-coding rna in lung cancer metastasis: a systematic review

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DISCOVER ONCOLOGY 2025年第1期16卷 1-23页

作者： Yang, Jie Luo, Yi Yao, Zuhuan Wang, Zhaokai Jiang, Ke Huazhong Univ Sci & Technol Union Hosp Tongji Med Coll Dept Thorac Surg 1277 Jiefang Ave Wuhan 430022 Hubei Peoples R China Guizhou Med Univ Clin Med Coll Guiyang 550004 Peoples R China

Lung cancer is one of the deadliest malignancies worldwide, with distant metastasis being a major cause of death. However, the specific mechanisms of lung cancer metastasis remain unclear. Ncrnas, a widely present type of non-coding rnas in the body, constitute about 98% of the human genome, lacking protein-coding capacity but involved in various cellular processes such as proliferation, apoptosis, invasion, and migration. Studies have shown that ncrnas play a crucial role in the metastasis of lung cancer, although research in this area is limited. This review summarizes the biological origins and functions of ncrnas, their specific roles and mechanisms in lung cancer metastasis, and discusses their potential for early screening and therapeutic applications in lung cancer. Furthermore, it outlines the challenges in translating basic advancements of ncrnas in lung cancer metastasis into clinical practice.

关键词： Lung cancer Metastasis non-coding rna Microrna Long non-coding rna Circular rna

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Long non-coding rna MIR22HG Alleviates Ischemic Acute Kidney Injury by Targeting the miR-134-5p/NFAT5 axis

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INFLAMMATION 2025年 1-14页

作者： Li, Jingdong Dong, Zhe Tang, Liting Liu, Lu Su, Cuijing Yu, Shan Sun Yat Sen Univ Affiliated Hosp 7 Dept Emergency & Disaster Med Ctr Shenzhen 518107 Guangdong Peoples R China Shenyang Fourth Peoples Hosp Dept Crit Care Med Shenyang 110083 Liaoning Peoples R China Shenyang Sujiatun Dist Cent Hosp Dept Emergency Shenyang 110100 Liaoning Peoples R China Sun Yat sen Univ Affiliated Hosp 7 Dept Gen Med 628 Zhenyuan RdXinhu St Shenzhen 518107 Guangdong Peoples R China

Acute kidney injury (AKI), often triggered by ischemia-reperfusion (I/R) injury, is a critical condition characterized by rapid loss of renal function, leading to high morbidity and mortality. Despite extensive research, therapeutic options for ischemic AKI remain limited, and understanding the molecular mechanisms involved is crucial for developing targeted therapies. Long non-coding rnas (lncrnas) have emerged as pivotal regulators of gene expression and cellular processes in various diseases, including cancer and renal injury. This study investigates the role of the lncrna MIR22HG in mitigating renal injury during ischemic AKI. Using in vivo and in vitro models of I/R-induced AKI in mice and hypoxia/reoxygenation (H/R)-treated renal cells, we demonstrated that MIR22HG expression is significantly downregulated in ischemic AKI conditions. Functional assays showed that overexpression of MIR22HG in these models led to reduced renal cell apoptosis, inflammation, and improved renal function. Mechanistically, MIR22HG exerted its protective effects by negatively regulating miR-134-5p, which in turn alleviated renal injury by upregulating NFAT5, a transcription factor known to mitigate cellular stress. Furthermore, dual-luciferase and rna pull-down assays confirmed direct interactions between MIR22HG and miR-134-5p, as well as miR-134-5p and NFAT5. Additionally, loss-and-gain-of-function assays demonstrated that overexpression of MIR22HG led to the upregulation of NFAT5, which mitigated renal apoptosis, and inflammation and improved renal function. Collectively, the results of our study highlight the therapeutic potential of targeting the MIR22HG/miR-134-5p/NFAT5 axis in the treatment of ischemic AKI, providing new insights into the molecular regulation of renal cell survival and repair during injury.

关键词： Ischemic acute kidney injury non-coding rna Mirna Renal inflammation Apoptosis

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Research progress of non-coding rna regulating the role of PANoptosis in diabetes mellitus and its complications

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APOPTOSIS 2025年第3-4期30卷 516-536页

作者： Han, Guangyu Hu, Kaibo Luo, Tianfeng Wang, Wenting Zhang, Deju Ouyang, Liu Liu, Xiao Liu, Jianping Wu, Yuting Liang, Jianqi Ling, Jitao Chen, Yixuan Xuan, Rui Zhang, Jing Yu, Peng Nanchang Univ Affiliated Hosp 2 Dept Endocrinol & Metab Nanchang 330006 Peoples R China Nanchang Univ Clin Med Coll 2 Nanchang 330006 Peoples R China Chinese Acad Med Sci & Peking Union Med Coll Fuwai Hosp Natl Ctr Cardiovasc Dis Dept Cardiol Beijing 100037 Peoples R China Hainan Med Univ Affiliated Hosp 2 Dept Anesthesiol Haikou 571199 Peoples R China Univ Hong Kong Sch Biol Sci Ood & Nutr Sci Pokfulam Rd Hong Kong Peoples R China Georgia State Univ Ctr Mol & Translat Med 157 Decatur St SE Atlanta GA 30303 USA Sun Yat Sen Univ Sun Yat Sen Mem Hosp Dept Cardiol Guangzhou Guangdong Peoples R China Nanchang Univ Affiliated Hosp 2 Dept Anesthesiol Nanchang 330006 Peoples R China

Diabetes is a chronic metabolic disease that is endemic worldwide and is characterized by persistent hyperglycemia accompanied by multiple severe complications, including cardiovascular disease, kidney dysfunction, neuropathy, and retinopathy. The pathogenesis of diabetes mellitus and its complications is multifactorial, involving various molecular and cellular pathways. In recent years, research has indicated that mechanisms of cell death play a significant role in the advancement of diabetes and its complications. PANoptosis is a complex phenomenon caused by three cell death pathways: programmed apoptosis, necroptosis and pyroptosis. The contribution of PANoptosis to diabetes and its complications remains incompletely understood. non-coding rna, an important molecule in gene expression regulation, has shown significant regulatory functions in a variety of diseases. This paper reviews the underlying mechanisms of diverse types of non-coding rnas (including lncrna, mirna and circrna) in regulating PANoptosis and their specific contributions in diabetes, aiming to explore how non-coding rnas influence PANoptosis and their effects in diabetes.

关键词： PANoposis Diabetes mellitus Diabetic complications non-coding rna

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Comprehensive analysis of long non-coding rna and mrna expression patterns during seminiferous tubules maturation in Guanzhong dairy goats

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BMC GENOMICS 2025年第1期26卷 1-17页

作者： Ren, Fa Zhang, Que Jiang, Yu Xie, Wenling Qiao, Pengyun Hu, Jianhong Shandong Second Med Univ Affiliated Hosp Dept Reprod Med Weifang Shandong Peoples R China Shandong Vocat Anim Sci & Vet Coll Dept Anim Sci & Technol Weifang 261061 Shandong Peoples R China Northwest A&F Univ Coll Anim Sci & Technol Key Lab Anim Genet Breeding & Reprod Shaanxi Prov 22 Xinong Rd Yangling 712100 Shaanxi Peoples R China

Background Long non-coding rnas (lncrnas) play crucial roles in testicular development and spermatogenesis. The seminiferous tubule, the exclusive site of spermatogenesis, houses all types of male germ cells, regulated by both lncrnas and mrnas. However, the expression patterns and functions of these molecules across different developmental stages of dairy goat seminiferous tubules remain poorly understood. Results In this study, we sequenced and identified lncrnas and mrnas expressed in the seminiferous tubules of Guanzhong dairy goats at two developmental stages: 45-day-old premature (G45) and 240-day-old mature (G240). Significant differences in testis index and seminiferous tubules morphology were observed between G45 and G240 (P < 0.05). Transcriptome analyses revealed 11,612 lncrnas and 18,217 mrnas, with 7,554 lncrnas and 11,986 mrnas showing significant differential expression between the two stages. Among these, 229 differentially expressed mrnas related to spermatogenesis were identified. Key genes, such as Kit, Dmrt1, and Sox9, were down-regulated, whereas Ddx4, Sycp1, and Sycp3 were up-regulated after sexual maturity. Notably, signalling pathways including PI3K/Akt, MAPK, and Rap1 were implicated in the regulation of spermatogenesis. We constructed lncrna-mrna interaction networks, identifying specific lncrnas and their target genes potentially critical for spermatogenesis. Additionally, single-cell transcriptome data validated the expression of key genes, revealing that Piwil4 and Dnmt3l were specifically expressed in spermatogonial clusters, whereas Piwil1, Piwil2, and Gtsf1 were predominantly expressed in spermatocyte clusters. Conclusions These findings highlight the essential roles of specific genes in the maturation of seminiferous tubules in dairy goats. This study provides comprehensive transcriptomic profiles and lncrna-mrna interaction networks between the G45 and G240 stages, offering valuable insights into spermatogenesis and seminiferous tub

关键词： non-coding rna Seminiferous tubules rna-sequencing Spermatogenesis Dairy goat

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Upregulation of long non-coding rna ENSG00000267838 is related to the high risk of progression and non-response to chemoradiotherapy treatment for cervical cancer

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non-coding rna RESEARCH 2025年第1期11卷 104-114页

作者： Duarte, Bruna Custodio Dias Queiroz, Fabio Ribeiro Costa, Alvaro Percinio Neto, Angelo Borges de Melo Melo, Carolina Pereira de Souza Salles, Paulo Guilherme de Oliveira Jeremias, Wander de Jesus Bertarini, Pedro Luiz Lima Amaral, Laurence Rodrigues do Braga, Leticia da Conceicao Gomes, Matheus de Souza Filho, Agnaldo Lopes da Silva Univ Fed Uberlandia Lab Bioinformat & Anal Mol BR-38702178 Patos De Minas MG Brazil Inst Mario Penna Lab Pesquisa Translac Oncol BR-30380490 Belo Horizonte MG Brazil Univ Fed Ouro Preto Escola Farm Lab Farmacol Expt BR-35402163 Ouro Preto MG Brazil Univ Fed Minas Gerais Fac Med Programa Posgrad Ciencias Aplicadas Cirurgia & Oft BR-31270901 Belo Horizonte MG Brazil

Cervical cancer (CC) is a global public health concern, primarily caused by persistent infection with oncogenic types of human papillomavirus (HPV). The World Health Organization (WHO) has established a plan to eliminate CC as a public health issue by the year 2100. However, the implementation of the HPV vaccine is impeded by vaccine restrictions and misinformation despite its demonstrated effectiveness. The CC treatment is influenced by the disease stage, with an unfavorable prognosis for those in advanced stages. This study aimed to investigate the potential of long non-coding rnas (lncrnas) in CC by identifying and characterizing related lncrnas, elucidating their regulatory mechanisms and molecular interactions, and analyzing their expression patterns in patients with diverse responses to chemoradiotherapy. non-stem cells from CC were isolated using flow cytometry sorting and used for total rna extraction. The rna was used to build libraries that were subsequently sequenced using the Illumina Nextseq 550.417 lncrnas that showed differentially expressed between CC patients who responded or not to treatment. Further analysis demonstrated that these lncrnas significantly interact with several molecules, which play crucial roles in CC progression and therapeutic resistance. Statistical analysis correlated the expression profile of these lncrnas with treatment efficacy. Three lncrnas, ENSG00000267838, ENSG00000266340, and FRMD6-AS1, were identified with positive expression related to non-response to chemoradiotherapy and worse progression-free survival in CC patients. Specifically, lncrna ENSG00000267838 has its up-regulation related to non-response and down-regulation to response to chemoradiotherapy treatment.

关键词： Gene expression Regulatory profile Biomarkers non-coding rna Cervical cancer Prognosis

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Chromosome-scale genome assembly reveals how repeat elements shape non-coding rna landscapes active during newt limb regeneration

CELL GENOMICS

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CELL GENOMICS 2025年第2期5卷 100761-100761页

作者： Brown, Thomas Mishra, Ketan Elewa, Ahmed Iarovenko, Svetlana Subramanian, Elaiyaraja Araus, Alberto Joven Petzold, Andreas Fromm, Bastian Friedlander, Marc R. Rikk, Lennart Suzuki, Miyuki Suzuki, Ken-ichi T. Hayashi, Toshinori Toyoda, Atsushi Oliveira, Catarina R. Osipova, Ekaterina Leigh, Nicholas D. Yun, Maximina H. Simon, Andras Tech Univ Dresden DRESDEN Concept Genome Ctr DcGC Ctr Mol & Cellular Bioengn Dresden Germany Max Planck Inst Mol Cell Biol & Genet D-01307 Dresden Germany Karolinska Inst Dept Cell & Mol Biol S-17165 Stockholm Sweden Augsburg Univ Dept Biol Minneapolis MN 55454 USA Tech Univ Dresden CRTD Ctr Regenerat Therapies Dresden D-01307 Dresden Germany UiT Arctic Univ Norway Arctic Univ Museum Norway N-9006 Tromso Norway Stockholm Univ Wenner Gren Inst Dept Mol Biosci Sci Life Lab S-11418 Stockholm Sweden Lund Univ Lund Stem Cell Ctr Wallenberg Ctr Mol Med Mol Med & Gene Therapy Lund Sweden CALTECH Div Biol & Biol Engn Pasadena CA 91125 USA Natl Inst Basic Biol Trans Scale Biol Ctr Emerging Model Organisms Facil Okazaki Aichi 4448585 Japan Hiroshima Univ Grad Sch Integrated Sci Life Program Biomed Sci Higashihiroshima Hiroshima 7398511 Japan Hiroshima Univ HiSIM Res Ctr Higashihiroshima Hiroshima 7398511 Japan Natl Inst Genet Dept Genom & Evolutionary Biol Comparat Genom Lab Mishima Shizuoka 4110801 Japan LOEWE Ctr Translat Biodivers Genom Senckenberganlage 25 D-60325 Frankfurt Germany Tech Univ Dresden D-01062 Dresden Germany

Newts have large genomes harboring many repeat elements. How these elements shape the genome and relate to newts' unique regeneration ability remains unknown. We present here the chromosome-scale assembly of the 20.3 Gb genome of the Iberian ribbed newt, Pleurodeles waltl, with a hitherto unprecedented contiguity and completeness among giant genomes. Utilizing this assembly, we demonstrate conserved synteny as well as genetic rearrangements, such as in the major histocompatibility complex locus. We provide evidence suggesting that intronic repeat elements drive newt-specific circular rna (circrna) biogenesis and show their regeneration-specific expression. We also present a comprehensive in-depth annotation and chromosomal mapping of micrornas, highlighting genomic expansion profiles as well as a distinct regulatory pattern in the regenerating limb. These data reveal links between repeat elements, non-coding rnas, and adult regeneration and provide key resources for addressing developmental, regenerative, and evolutionary principles.

关键词： amphibian salamander giant genome regeneration blastema microrna circular rna non-coding rna transposable element PacBio

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