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Exploring the role of LINC-ROR in epithelial-mesenchymal transition and its correlation with CD44 and TWIST1 in gastric cancer progression

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HUMAN GENE 2025年 44卷

作者： Mahmoudian, Reihaneh Alsadat Golyan, Fatemeh Fardi Forghanifard, Mohammad Mahdi Gholamin, Mehran Mansouri, Atena Tanzadehpanah, Hamid Abbaszadegan, Mohammad Reza Mashhad Univ Med Sci Metab Syndrome Res Ctr Mashhad Iran Mashhad Univ Med Sci Canc Res Ctr Mashhad Iran Islamic Azad Univ Dept Biol Damghan Branch Damghan Iran Mashhad Univ Med Sci Sch Paramed Sci Dept Lab Sci Mashhad Iran Mashhad Univ Med Sci Immunol Res Ctr Mashhad Iran Birjand Univ Med Sci Cellular & Mol Res Ctr Birjand Iran Mashhad Univ Med Sci Basic Sci Res Inst Antimicrobial Resistance Res Ctr Mashhad Iran Mashhad Univ Med Sci Med Genet Res Ctr Mashhad Iran Mashhad Univ Med Sci Fac Med Dept Med Genet Mashhad Iran

Background: Gastric cancer (GC) is a leading cause of cancer-related mortality, characterized by its intricate etiology and aggressive nature. The interplay between coding and non-coding rnas facilitates the identification of protein-protein interaction networks, which are crucial for understanding the prognosis, incidence, diagnosis, and treatment of cancer. This study aims to investigate the clinical significance of co-expression of lncrna regulator of reprogramming (LINC-ROR), TWIST1, and CD44 in GC, offering valuable insights into the disease's pathogenesis and potential therapeutic targets. Materials and methods: Quantitative real-time PCR was employed to compare the expression profiles of LINC-ROR, TWIST1, and CD44 in 86 paired tumor and adjacent normal tissue samples obtained from GC patients who underwent curative surgery. The expression levels of LINC-ROR, TWIST1, and CD44 were canalyzed to evaluate their co-expression patterns and determine their clinical significance in GC. Results: Our findings demonstrated that the concomitant expression of LINC-ROR and CD44 was significantly correlated with lymph node invasion and early tumor stages (I/II) (P < 0.05). Moreover, the co-expression of LINC-ROR and CD44 with TWIST1 correlated with tumor grade II and stages I/II of tumor progression (P < 0.05). Notably, LINC-ROR was underexpressed in 54.7 % of tumors, while TWIST1 and CD44 were overexpressed in 53.5 % and 50 % of cases, respectively (P < 0.0001). The dysregulation of these markers was significantly linked to severalclinical factors, including sex, tumor stage, H. pylori, grade, type, and location of tumor (P < 0.05). Conclusion: Our findings emphasize the regulatory role of LINC-ROR in EMT processes and GC progression, highlighting its potential as a biomarker for prognosis and therapeutic targets in GC management. This study enhances our understanding of the icomplex molecular interactions that underlie GC pathogenesis.

关键词： non-coding rna Epithelial-mesenchymal transition LINC-ROR CD44 TWIST1

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Competing endogenous rnas(cernas)and drug resistance to cancer therapy

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Cancer Drug Resistance 2024年第1期7卷 357-381页

作者： Kenneth K.W.To Hang Zhang William C.Cho School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR 999077China Department of Clinical Oncology Queen Elizabeth HospitalHong Kong SAR 999077China

Competing endogenous rnas(cernas)are transcripts that possess highly similar microrna response elements(MREs).micrornas(mirnas)are short,endogenous,single-stranded non-coding rnas(ncrnas)that can repress gene expression by binding to MREs on the 3’untranslated regions(UTRs)of the target mrna transcripts to suppress gene expression by promoting mrna degradation and/or inhibiting protein *** transcripts,circular rnas(circrnas),long non-coding rnas(lncrnas),and transcribed pseudogenes could share similar MREs,and they can compete for the same pool of *** cernas may affect the level of one another by competing for their shared *** interplay between different rnas constitutes a cerna network,which regulates many important biological *** drug resistance is a major factor leading to treatment failure in patients receiving *** can be acquired through genetic,epigenetic,and various tumor microenvironment *** involvement of cerna crosstalk and its disruption in chemotherapy resistance is attracting attention in the cancer research *** review presents an updated summary of the latest research on cerna dysregulation causing drug resistance across different cancer types and chemotherapeutic drug ***,accumulating evidence suggests that cernas may be used as prognostic biomarkers to predict clinical response to cancer ***,detailed experimental investigations of the putative cerna networks generated by computational algorithms are needed to support their translation for therapeutic and prognostic applications.

关键词： Alternative mrna polyadenylation cancer immunotherapy cerna crosstalk immune evasion microrna mrna 3’untranslated region multidrug resistance non-coding rna

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Circ-calm4 regulates hypoxia-induced pulmonary artery smooth muscle autophagy by binding Purb

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JOUrnaL OF MOLECULAR AND CELLULAR CARDIOLOGY 2023年第1期176卷 41-54页

作者： Zhang, Junting Li, Yiying Chen, Yujie Yu, Xiufeng Wang, Shanshan Sun, Hanliang Zheng, Xiaodong Zhang, Lixin Wang, Yifan Zhu, Daling Harbin Med Univ Coll Pharm Harbin Peoples R China Harbin Med Univ Daqing Coll Med Lab Sci & Technol Harbin Peoples R China Harbin Med Univ Daqing Dept Pharmacol Harbin Peoples R China Harbin Med Univ Daqing Cent Lab Harbin Peoples R China State Prov Key Labs Biomed Pharmaceut China Harbin Peoples R China Harbin Med Univ Key Lab Cardiovasc Med Res Minist Educ Harbin Peoples R China Harbin Med Univ Daqing Coll Pharm Xinyang Rd Daqing 163319 Heilongjiang Peoples R China

Pulmonary hypertension (PH) is a serious and fatal disease characterized by pulmonary vasoconstriction and pulmonary vascular remodeling. The excessive autophagy of pulmonary artery smooth muscle cells (PASMCs) is one of the important factors of pulmonary vascular remodeling. A number of studies have shown that circular rna (circrna) can participate in the onset of PH. Our previous studies have shown that circrna calmodulin 4 (circ-calm4) is involved in the progression of hypoxic PH. However, the role of circ-calm4 on regulation of hypoxic PH autophagy has not been reported. In this study, we demonstrated for the first time that hypoxia-mediated upregulated circ-calm4 expression has a key regulatory effect on autophagy in hypoxia-induced PASMCs and hypoxic PH mouse models. Knockdown of circ-calm4 both in vivo and in vitro can inhibit the autophagy in PASMCs induced by hypoxia. We also performed bioinformatics predictions and conducted ex-periments to verify that circ-calm4 bound to the purine-rich binding protein (Purb) to promote its expression in the nucleus, thereby initiating the transcription of autophagy-related protein Beclin1. Interestingly, we found that Beclin1 transcription initiated by Purb was accompanied by a modification of Beclin1 super-enhancer to improve transcription activity and efficiency. Overall, our results confirm that the circ-calm4/Purb/Beclin1 signal axis is involved in the occurrence of hypoxia-induced PASMCs autophagy, and the novel regulatory mechanisms and signals transduction pathways in PASMC autophagy induced by hypoxia.

关键词： Autophagy circrna Hypoxia non-coding rna Pulmonary hypertension

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Advancements in understanding mechanisms of hepatocellular carcinoma radiosensitivity:A comprehensive review

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Chinese Journal of Cancer Research 2023年第3期35卷 266-282页

作者： Gaoyuan Yang Huamei Yan Yongchang Tang Feng Yuan Mingbo Cao Yupeng Ren Yuxuan Li Zhiwei He Xiaorui Su Zhicheng Yao Meihai Deng Department of Hepatobiliary Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of Radiation Oncology The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of General Surgery Qilu HospitalShandong UniversityJinan 250012China Department of General Surgery The First Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China Department of Hepatobiliary and Pancreatic Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China

Primary liver cancer is a significant health problem *** carcinoma(HCC)is the main pathological type of primary liver cancer,accounting for 75%-85%of *** recent years,radiotherapy has become an emerging treatment for HCC and is effective for various stages of ***,radiosensitivity of liver cancer cells has a significant effect on the efficacy of radiotherapy and is regulated by various *** to increase radiosensitivity and improve the therapeutic effects of radiotherapy require further *** review summarizes the recent research progress on the mechanisms affecting sensitivity to radiotherapy,including epigenetics,transportation and metabolism,regulated cell death pathways,the microenvironment,and redox status,as well as the effect of nanoparticles on the radiosensitivity of liver *** is expected to provide more effective strategies and methods for clinical treatment of liver cancer by radiotherapy.

关键词： Hepatocellular carcinoma radiosensitivity epigenetics non-coding rna cell death metabolism tumor microenvironment reactive oxygen species nanoparticle

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Functional variation in the non-coding genome: molecular implications for food security

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JOUrnaL OF EXPERIMENTAL BOTANY 2023年第7期74卷 2338-2351页

作者： Gullotta, Giorgio Korte, Arthur Marquardt, Sebastian Univ Copenhagen Copenhagen Plant Sci Ctr Dept Plant & Environm Sci Bulowsvej 21A DK-1871 Frederiksberg Denmark Univ Wurzburg Ctr Computat & Theoret Biol Hubland Nord 32 D-97074 Wurzburg Germany

Here we review compelling functional examples that highlight the implications of DNA sequence variation in the non-coding genome for plant biology and food production. The growing world population, in combination with the anticipated effects of climate change, is pressuring food security. Plants display an impressive arsenal of cellular mechanisms conferring resilience to adverse environmental conditions, and humans rely on these mechanisms for stable food production. The elucidation of the molecular basis of the mechanisms used by plants to achieve resilience promises knowledge-based approaches to enhance food security. DNA sequence polymorphisms can reveal genomic regions that are linked to beneficial traits of plants. However, our ability to interpret how a given DNA sequence polymorphism confers a fitness advantage at the molecular level often remains poor. A key factor is that these polymorphisms largely localize to the enigmatic non-coding genome. Here, we review the functional impact of sequence variations in the non-coding genome on plant biology in the context of crop breeding and agricultural traits. We focus on examples of non-coding with particularly convincing functional support. Our survey combines findings that are consistent with the view that the non-coding genome contributes to cellular mechanisms assisting many plant traits. Understanding how DNA sequence polymorphisms in the non-coding genome shape plant traits at the molecular level offers a largely unexplored reservoir of solutions to address future challenges in plant growth and resilience.

关键词： Arabidopsis crop epigenetics gene expression genome-wide association studies genomics non-coding genome non-coding rna regulation

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has_circ_0070512 promotes prostate cancer progression by regulating the miR-338-3p/hedgehog signaling pathway

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CANCER SCIENCE 2023年第4期114卷 1491-1506页

作者： Zhang, Pingxin Gao, Hang Yan, Ruping Yu, Lu Xia, Chengxing Yang, Delin Kunming Med Univ Dept Urol Affiliated Hosp 2 374 Yunnan Myanmar Ave Kunming 650101 Yunnan Peoples R China

Circular rnas (circrnas) are a type of non-coding rna that plays a vital role in biology. circrnas appear to have a role in the development and progression of several malignancies, according to research. However, circrnas that regulate prostate cancer (PCa) progression are still largely unknown and deserve further exploration. The aim of this study was to investigate the effect of hsa_circ_0070512 on the function and mechanism of PCa. hsa_circ_0070512 was increased in PCa tissues and cells and was mostly found in the cytoplasm of PCa cells. Overexpression of hsa_circ_0070512 considerably increased PCa cell proliferation and migration, whereas silencing of hsa_circ_0070512 greatly decreased PCa cell proliferation and migration. Mechanistically, we show that hsa_circ_0070512 acts as a "molecular sponge" for miR-338-3p and that the miR-338-3p mimics partially block the pro-tumor effects of hsa_circ_0070512. rna sequencing analysis of PC3 cells stably overexpressing hsa_circ_0070512 revealed that hedgehog was downstream of the signaling pathways of hsa_circ_0070512 and miR-338-3p. Our results implied that hsa_circ_0070512 regulated the hedgehog signaling pathways through miR-338-3p to enhance PCa growth and migration, providing a new diagnostic and therapeutic target for PCa.

关键词： biomarker circular rna mirna non-coding rna prostate cancer

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Emerging roles of Circrna-mirna networks in cancer development and therapeutic response

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non-coding rna RESEARCH 2025年第1期10卷 98-115页

作者： Hashemi, Mehrdad Khosroshahi, Elaheh Mohandesi Daneii, Pouria Hassanpoor, Aria Eslami, Maedeh Koohpar, Zeinab Khazaei Asadi, Saba Zabihi, Abbas Jamali, Behdokht Ghorbani, Amin Nabavi, Noushin Memarkashani, Mohammad Reza Salimimoghadam, Shokooh Taheriazam, Afshin Tan, Shing Cheng Entezari, Maliheh Farahani, Najma Hushmandi, Kiavash Islamic Azad Univ Fac Adv Sci & Technol Dept Genet Tehran Med Sci Tehran Iran Islamic Azad Univ Farhikhtegan Hosp Tehran Med Sci Farhikhtegan Med Convergence Sci Res Ctr Tehran Iran Islamic Azad Univ Fac Biol Sci Dept Cell & Mol Biol Tonekabon Branch Tonekabon Iran Islamic Azad Univ Fac Basic Sci Dept Biol Hamedan Branch Hamadan Iran Kherad Inst Higher Educ Dept Microbiol & Genet Bushehr Iran Islamic Azad Univ Dept Clin Sci Sci & Res Branch Tehran Iran Shahid Chamran Univ Ahvaz Fac Vet Med Dept Biochem & Mol Biol Ahvaz Iran Islamic Azad Univ Fac Med Dept Orthoped Tehran Med Sci Tehran Iran Univ Kebangsaan Malaysia UKM Med Mol Biol Inst Kuala Lumpur Malaysia Univ Tehran Fac Vet Med Dept Epidemiol Tehran Iran

The complex interplay of epigenetic factors is essential in regulating the hallmarks of cancer and orchestrating intricate molecular interactions during tumor progression. Circular rnas (circrnas), known for their covalently closed loop structures, are non-coding rna molecules exceptionally resistant to enzymatic degradation, which enhances their stability and regulatory functions in cancer. Similarly, micrornas (mirnas) are endogenous noncoding rnas with linear structures that regulate cellular biological processes akin to circrnas. Both mirnas and circrnas exhibit aberrant expressions in various cancers. Notably, circrnas can function as sponges for mirnas, influencing their activity. The circrna/mirna interaction plays a pivotal role in the regulation of cancer progression, including in brain, gastrointestinal, gynecological, and urological cancers, influencing key processes such as proliferation, apoptosis, invasion, autophagy, epithelial-mesenchymal transition (EMT), and more. Additionally, this interaction impacts the response of tumor cells to radiotherapy and chemotherapy and contributes to immune evasion, a significant challenge in cancer therapy. Both circrnas and mirnas hold potential as biomarkers for cancer prognosis and diagnosis. In this review, we delve into the circrna-mirna circuit within human cancers, emphasizing their role in regulating cancer hallmarks and treatment responses. This discussion aims to provide insights for future research to better understand their functions and potentially guide targeted treatments for cancer patients using circrna/mirna-based strategies.

关键词： Circrna mirna Cancer therapy Chemoresistance non-coding rna

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New insights into diabetes-induced cardiac pathology

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JOUrnaL OF MOLECULAR AND CELLULAR CARDIOLOGY 2025年 203卷 76-81页

作者： Weeks, K. L. Bernardo, B. C. Bell, J. R. Delbridge, L. M. D. Mellor, K. M. Univ Melbourne Dept Anat & Physiol Melbourne Vic Australia Univ Melbourne Dept Cardiometab Hlth Melbourne Vic Australia Monash Univ Cent Clin Sch Dept Diabet Melbourne Vic Australia Deakin Univ Inst Phys Act & Nutr Sch Exercise & Nutr Sci Melbourne Vic Australia La Trobe Univ Dept Microbiol Anat Physiol & Pharmacol Melbourne Vic Australia Univ Auckland Dept Physiol Auckland New Zealand

Individuals with diabetes have an elevated risk of heart disease, and there is a significant clinical need for evidence-based treatments. Heart disease in diabetes manifests as a distinct cardiopathology, with cardiac structural and functional remodeling underlying increased susceptibility to cardiac dysfunction and arrhythmias. An understanding of the mechanisms associated with cardiac vulnerability in diabetes is incomplete, but recent studies have advanced new insights into the roles of metabolic disturbances, gene dysregulation and epicardial adipose influence. This perspective article highlights these three promising new developments in proposed mechanisms, and discusses exciting advances in cardiac-targeting for potential treatment of diabetic heart disease.

关键词： Diabetic heart disease Cardiac metabolism non-coding rna Cardiac gene delivery Epicardial adipose Adeno-associated viral vector

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Exosomes derived let-7f-5p is a potential biomarker of SLE with anti-inflammatory function

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non-coding rna RESEARCH 2025年 12卷 116-131页

作者： Liu, Yi-jing Miao, Hai-bing Lin, Shu Chen, Zhen Fujian Med Univ Affiliated Hosp 2 Dept Rheumatol & Immunol Quanzhou Fujian Peoples R China Fujian Med Univ Affiliated Hosp 2 Ctr Neurol & Metab Res Quanzhou Fujian Peoples R China Garvan Inst Med Res Grp Neuroendocrinol Sydney Australia

This study found that in patients with SLE (n = 5), lethal (let)-7f-5p expression was significantly downregulated in peripheral blood mononuclear cells. Further, high-throughput rna sequencing was used to mine the differential transcriptome expression in renal tissue exosomes of systemic lupus erythematosus (SLE)-prone mice, and bioinformatics was utilized to analyze non-coding rnas and coding rnas in exosomes for their possible roles in SLE. In renal tissues of MRL/lpr SLE-prone mice with exosomes and Pristane-induced SLE mice, we also demonstrated aberrant expression levels of microrna (mirna) let-7f-5p. Meanwhile, in the macrophage inflammation model, the expression levels of let-7f-5p were downregulated, that of guanylate binding protein (Gbp2 and Gbp7) were upregulated, and the inflammatory state of macrophages was alleviated following transfection with the let-7f-5p mimic. Co-culturing mesenchymal stem cells with a macrophage model of inflammation resulted in increased let-7f-5p expression and downregulated inflammatory factors, Gbp2 and Gbp7 expression in macrophages. Dual luciferase reporter gene assays confirmed that let-7f-5p directly binds to the 3 ' UTR of Gbp7 to regulate its expression. Let-7f-5p regulation of the Gbp family is involved in SLE pathogenesis and is a biomarker associated with the inflammatory response with potential clinical applications.

关键词： Systemic lupus erythematosus Exosomes non-coding rna

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Epigenetics in developmental defects of enamel: A scoping review

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ORAL DISEASES 2023年第6期29卷 2366-2375页

作者： Zhang, Yi Li, Hongyu Cui, Dixin Liu, Yi Tian, Qinglu Zheng, Liwei Wan, Mian Sichuan Univ West China Hosp Stomatol Natl Clin Res Ctr Oral Dis Dept Pediat DentState Key Lab Oral Dis Chengdu Peoples R China Sichuan Univ State Key Lab Oral Dis West China Hosp Stomatol Chengdu Peoples R China Sichuan Univ Natl Clin Res Ctr Oral Dis West China Hosp Stomatol Chengdu Peoples R China Sichuan Univ West China Hosp Stomatol Dept Cariol & Endodont Chengdu Peoples R China 14 Renmin South Rd 3rd Sect Chengdu 610041 Peoples R China

Objectives: The significant role of epigenetics has been revealed in normal enamel formation process and occurrence of developmental defects. This presented literature is aiming at summarizing the regulatory function of epigenetics in physiological amelogenesis process and reviewing the epigenetic mechanisms in occurrence of developmental defects of enamel (DDE), so as to provide biological foundation evidence to support early predication and clinical management of ***: An extensive literature review was conducted using electronic databases MEDLINE (through PubMed), Web of Science and EMBASE up to November 30, 2022. Studies about epigenetic effects on enamel tissue or cells associated with amelogenesis, including in vivo studies using human or animal models, and in vitro studies, are ***: A total of 22 studies were included. Epigenetic factors or effects specifically activate or silence certain genes, which may regulate related biological activities including cell proliferation, cell differentiation, enamel secretion, and mineralization during the process of amelogenesis. Once the status of epigenetic modification is altered, the quantity and quality of enamel may both be disturbed, which can finally result in ***: Epigenetics plays a noteworthy role of regulating the amelogenesis process and DDE potentially by altering the expression levels of genes related to enamel formation, providing a new perspective of early predication and clinical management of DDE.

关键词： amelogenesis developmental defects of enamel DNA methylation epigenetics histone modification non-coding rna

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