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MicroRNAs modulation in lung cancer: exploring dual mechanisms and clinical prospects

BIOCELL 2024年第3期48卷 403-413页

作者： SHAHID HUSSAIN HABIB BOKHARI XINGXING FAN SHAUKAT IQBAL MALIK SUNDAS IJAZ MUHAMMAD ADNAN SHEREEN AIMAN FATIMA Department of Biotechnology Kohsar University MurreeMurreePakistan Macao University of Science and Technology State Key Laboratory of Quality Research in Chinese Medicines TaipaMacao Department of Bioinformatics and Biosciences Capital University of Science and TechnologyIslamabadPakistan Department of Microbiology Kohsar University MurreeMurreePakistan

The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal inﬂuence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversiﬁed impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the speciﬁc miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.

关键词： miRNAs oncogenes Tumor suppressive genes Lung cancer therapy

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Critical involvement of circular RNAs in virus-associated cancers

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Genes & Diseases 2023年第6期10卷 2296-2305页

作者： Arghavan Zebardast Tayebeh Latifi Moein shirzad Golnaz Goodarzi Saeed Ebrahimi Fana Sadra Samavarchi Tehrani Yousef Yahyapour Department of Virology School of Public HealthTehran University of Medical SciencesTehran ***Iran Cellular and Molecular Biology Research Center Health Research InstituteBabol University of Medical SciencesBabol 47176Iran Department of Clinical Biochemistry School of MedicineTehran University of Medical SciencesTehran ***Iran Student Scientific Research Center Tehran University of Medical SciencesTehran ***Iran Infectious Diseases and Tropical Medicine Research Center Health Research InstituteBabol University of Medical SciencesBabol 47176Iran

Virus-related cancer is cancer where viral infection leads to the malignant transformation of the host's infected cells. Seven viruses (e.g., human papillomavirus (HPV), Epstein–Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human T-lymphotropic virus (HTLV), and Merkel cell polyomavirus (MCV)) that infect humans have been identified as an oncogene and have been associated with several human malignancies. Recently, growing attention has been attracted to exploring the pathogenesis of virus-related cancers. One of the most mysterious molecules involved in carcinogenesis and progression of virus-related cancers is circular RNAs (circRNA). These emerging non-coding RNAs (ncRNAs), due to the absence of 5′ and 3′ ends, have high stability than linear RNAs and are found in some species across the eukaryotic organisms. Compelling evidence has revealed that viruses also encode a repertoire of circRNAs, as well as dysregulation of these viral circRNAs play a critical role in the pathogenesis and progression of different types of virus-related cancers. Therefore, understanding the exact role and function of the virally encoded circRNAs with virus-associated cancers will open a new road for increasing our knowledge about the RNA world. Hence, in this review, we will focus on emerging roles of virus-encoded circRNAs in multiple cancers, including cervical cancer, gastric cancer, Merkel cell carcinoma, nasopharyngeal carcinoma, Kaposi cancer, and liver cancer.

关键词： Cancer Circular RNA Neoplasms oncogenes Viruses

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oncogenes, oncogenesis, and Oxygen Radicals

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Biomedical and Environmental Sciences 1990年第2期3卷 183-201页

作者： SAURA C.SAHU Molecular Toxicology Laboratory Division of Toxicological Studies Food and Drug Administration Washington D.C. 20204

The role that free radicals in general and oxygen radicals in particular play in carcinogenesis has attracted considerable attention in recent years. The oxygen radicals are undesirable but inevitable products of aerobic metabolism in the normal living cell. The cellular antioxidant defense system maintains an appropriate balance between necessary oxidative events and those that are excessive. When this critical balance cannot be maintained because of the overloading of the cellularredox system, oxygen radicals can induce cell damage. They can influence carcinogenesis by inducing DN A damage from direct oxidation or indirectly from DNA-binding products of lipid peroxidation. Oxygen radicals can induce conformational changes in the plasma membrane by lipid peroxidation and protein degradation, thus influencing membrane-associated cellular activities. They are capable of affecting membrane-bound protein kinases, growth factors and their receptors, and, therefore, signal transduction and oncogene activation. Thus, the oxygen radicals can have a major influence on oncogenes and oncogenesis. (C)1990 Academic Press.Inc.

关键词： gene and Oxygen Radicals oncogenes oncogenesis

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Integrated transcriptome interactome study of oncogenes and tumor suppressor genes in breast cancer

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Genes & Diseases 2019年第1期6卷 78-87页

作者： G.Pranavathiyani Raja Rajeswary Thanmalagan Naorem Leimarembi Devi Amouda Venkatesan Centre for Bioinformatics School of Life SciencesPondicherry UniversityPondicherry 605014India

Breast cancer is the leading cause for mortality among women worldwide.Dysregulation of oncogenes and tumor suppressor genes is the major reason for the cause of cancer.Understanding these genes will provide clues and insights about their regulatory mechanism and their interplay in cancer.In the present study,an attempt is made to compare the functional characteristics and interactions of oncogenes and tumor suppressor genes to understand their biological role.431 breast cancer samples from seven publicly available microarray datasets were collected and analysed using GEO2R tool.The identified 416 differentially expressed genes were classified into five gene sets as oncogenes(OG),tumor suppressor genes(TSG),druggable genes,essential genes and other genes.The gene sets were subjected to various analysis such as enrichment analysis(viz.,GO,Pathways,Diseases and Drugs),network analysis,calculation of mutation frequencies and Guanine-Cytosine(GC)content.From the results,it was observed that the OG were having high GC content as well as high interactions than TSG.Moreover,the OG are found to have frequent mutations than TSG.The enrichment analysis results suggest that the oncogenes are involved in positive regulation of cellular protein metabolic process,macromolecule biosynthetic process and majorly in cell cycle and focal adhesion pathway in cancer.It was also found that these oncogenes are involved in other diseases such as skin diseases and viral infections.Collagenase,paclitaxel and docetaxel are some of the drugs found to be enriched for oncogenes.

关键词： Breast cancer Differential gene expression Network analysis oncogenes Tumor suppressor genes

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Special　Reports　and　Review　oncogenes　AND　CELL　IMMUNOGENITY：v－H－ras　SUPPRESSING　MHC　CLASS　I　EXPRESSION　IN　MOUSE　FIBROBLAST

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Chinese Journal of Cancer Research 1994年第2期6卷 149-156页

作者：吕有勇

ＳｐｅｃｉａｌＲｅｐｏｒｔｓａｎｄＲｅｖｉｅｗＯＮＣＯＧＥＮＥＳＡＮＤＣＥＬＬＩＭＭＵＮＯＧＥＮＩＴＹ：ｖ－Ｈ－ｒａｓＳＵＰＰＲＥＳＳＩＮＧＭＨＣＣＬＡＳＳＩＥＸＰＲＥＳＳＩＯＮＩＮＭＯＵＳＥＦＩＢＲＯＢＬＡＳＴＬｕ... 详细信息

ＳｐｅｃｉａｌＲｅｐｏｒｔｓａｎｄＲｅｖｉｅｗＯＮＣＯＧＥＮＥＳＡＮＤＣＥＬＬＩＭＭＵＮＯＧＥＮＩＴＹ：ｖ－Ｈ－ｒａｓＳＵＰＰＲＥＳＳＩＮＧＭＨＣＣＬＡＳＳＩＥＸＰＲＥＳＳＩＯＮＩＮＭＯＵＳＥＦＩＢＲＯＢＬＡＳＴＬｕＹｏｕｙｏｎｇ；吕有勇；Ｓｈｒａｇ...

关键词： CLASS CELL AND EXPRESSION FIBROBLAST IMMUNOGENITY IN MHC MOUSE oncogenes

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Molecular genetics of early-onset colorectal cancer

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World Journal of Biological Chemistry 2023年第2期14卷 13-27页

作者： Olivia Marx Marc Mankarious Gregory Yochum Department of Biochemistry&Molecular Biology Pennsylvania State University College of MedicineHersheyPA 17033United States Department of Surgery Division of Colon&Rectal SurgeryPennsylvania State University Milton S.Hershey Medical CenterHersheyPA 17033United States Department of Biochemistry&Molecular Biology&Surgery Pennsylvania State University College of MedicineHersheyPA 17033United States

Early-onset colorectal cancer(EOCRC)has been rising in global prevalence and incidence over the past several decades.Environmental influences,including generational lifestyle changes and rising obesity,contribute to these increased rates.While the rise in EOCRC is best documented in western countries,it is seen throughout the world,although EOCRC may have distinct genetic mutations in patients of different ethnic backgrounds.Pathological and molecular characterizations show that EOCRC has a distinct presentation compared with later-onset colorectal cancer(LOCRC).Recent studies have identified DNA,RNA,and protein-level alterations unique to EOCRC,revealing much-needed biomarkers and potential novel therapeutic targets.Many molecular EOCRC studies have been performed with Caucasian and Asian EOCRC cohorts,however,studies of other ethnic backgrounds are limited.In addition,certain molecular characterizations that have been conducted for LOCRC have not yet been repeated in EOCRC,including high-throughput analyses of histone modifications,mRNA splicing,and proteomics on large cohorts.We propose that the complex relationship between cancer and aging should be considered when studying the molecular underpinnings of EOCRC.In this review,we summarize current EOCRC literature,focusing on sporadic molecular alterations in tumors,and their clinical implications.We conclude by discussing current challenges and future directions of EOCRC research efforts.

关键词： Early-onset colorectal cancer Later-onset colorectal cancer Mutations oncogenes Molecular characteristics Transcriptomics

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Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2738-2748页

作者： Kailin Li Jieqiong You Qian Wu Wen Meng Qiaojun He Bo Yang Chengliang Zhu Ji Cao College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310058China Affiliated Hangzhou First People’s Hospital Zhejiang University School of MedicineHangzhou 310058China Cancer Center of Zhejiang University Hangzhou 310058China

Synthetic lethality is a proven effective antitumor strategy that has attracted great attention.Large-scale screening has revealed many synthetic lethal genetic phenotypes,and relevant smallmolecule drugs have also been implemented in clinical practice.Increasing evidence suggests that CDKs,constituting a kinase family predominantly involved in cell cycle control,are synthetic lethal factors when combined with certain oncogenes,such as MFC,TP53,and RAS,which facilitate numerous antitumor treatment options based on CDK-related synthetic lethality.In this review,we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future.

关键词： Synthetic lethality Cyclin-dependent kinase Antitumor therapy oncogenes MYC P53 RAS PARP

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Cytogenetic and molecular genetic alterations in hepatocellular carcinoma

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Acta Pharmacologica Sinica 2005年第6期26卷 659-665页

作者： Sze-hang LAU, Xin-yuan GUAN~1 Department of Clinical Oncology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China Department of Clinical Oncology Faculty of Medicine The University of Hong Kong Hong Kong China

Specific chromosome aberrations are frequently detected during the development of hepatocellular carcinoma. Molecular cytogenetic approaches such as comparative genomic hybridization and loss of heterozygosity analyses have provided fruitful information on changes in HCC cases at the genomic level. Mapping of chromosome gains and losses have frequently resulted in the identification of oncogenes and tumor suppressors, respectively. In this review, we summarize some frequently detected chromosomal aberrations reported for hepatocellular carcinoma cases using comparative genomic hybridization and loss of heterozygosity studies. Focus will be on gains of lq, 8q, and 20q, and losses of 4q, 8p, 13q, 16q, and 17p. We then examine the candidate oncogenes and tumor suppressors located within these regions, and explore their possible functions in hepatocarcinogenesis. Finally, the impact of microarray-based screening platforms will be discussed.

关键词： hepatocellular carcinoma chromosome aberrations oncogenes tumor suppressor genes

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AU-rich element-binding proteins in colorectal cancer

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World Journal of Gastrointestinal Oncology 2019年第2期11卷 71-90页

作者： Noémie Legrand Dan A Dixon Cyril Sobolewski Department of Microbiology Faculty of Medicine University of Geneva Department of Molecular Biosciences University of Kansas Lawrence Kansasand University of Kansas Cancer Center Department of Cell Physiology and Metabolism Faculty of MedicineUniversity of Geneva

Trans-acting factors controlling mRNA fate are critical for the post-transcriptional regulation of inflammation-related genes, as well as for oncogene and tumor suppressor expression in human cancers. Among them, a group of RNA-binding proteins called "Adenylate-Uridylate-rich elements binding proteins"(AUBPs)control mRNA stability or translation through their binding to AU-rich elements enriched in the 3'UTRs of inflammation-and cancer-associated mRNA transcripts. AUBPs play a central role in the recruitment of target mRNAs into small cytoplasmic foci called Processing-bodies and stress granules(also known as P-body/SG). Alterations in the expression and activities of AUBPs and Pbody/SG assembly have been observed to occur with colorectal cancer(CRC)progression, indicating the significant role AUBP-dependent post-transcriptional regulation plays in controlling gene expression during CRC tumorigenesis.Accordingly, these alterations contribute to the pathological expression of many early-response genes involved in prostaglandin biosynthesis and inflammation,along with key oncogenic pathways. In this review, we summarize the current role of these proteins in CRC development. CRC remains a major cause of cancer mortality worldwide and, therefore, targeting these AUBPs to restore efficient post-transcriptional regulation of gene expression may represent an appealing therapeutic strategy.

关键词： Colorectal cancer Adenylate-Uridylate-rich element-binding proteins oncogenes Tumor suppressors Post-transcriptional regulation

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Stress granules in colorectal cancer:Current knowledge and potential therapeutic applications

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World Journal of Gastroenterology 2020年第35期26卷 5223-5247页

作者： Noémie Legrand Dan A Dixon Cyril Sobolewski Department of Medicine Faculty of MedicineUniversity of GenevaGeneva CH-1211Switzerland Department of Molecular Biosciences University of KansasLawrenceKansasand University of Kansas Cancer CenterLawrenceKS 66045United States Department of Cell Physiology and Metabolism Faculty of MedicineUniversity of GenevaGeneva CH-1211Switzerland

Stress granules(SGs)represent important non-membrane cytoplasmic compartments,involved in cellular adaptation to various stressful conditions(e.g.,hypoxia,nutrient deprivation,oxidative stress).These granules contain several scaffold proteins and RNA-binding proteins,which bind to mRNAs and keep them translationally silent while protecting them from harmful conditions.Although the role of SGs in cancer development is still poorly known and vary between cancer types,increasing evidence indicate that the expression and/or the activity of several key SGs components are deregulated in colorectal tumors but also in pre-neoplastic conditions(e.g.,inflammatory bowel disease),thus suggesting a potential role in the onset of colorectal cancer(CRC).It is therefore believed that SGs formation importantly contributes to various steps of colorectal tumorigenesis but also in chemoresistance.As CRC is the third most frequent cancer and one of the leading causes of cancer mortality worldwide,development of new therapeutic targets is needed to offset the development of chemoresistance and formation of metastasis.Abolishing SGs assembly may therefore represent an appealing therapeutic strategy to re-sensitize colon cancer cells to anti-cancer chemotherapies.In this review,we summarize the current knowledge on SGs in colorectal cancer and the potential therapeutic strategies that could be employed to target them.

关键词： Stress-Granules Colorectal cancer Adenylate-Uridylate-rich element-binding proteins Post-transcriptional regulation oncogenes Tumor suppressors

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