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Identification of Proteins and Genes Associated with hedgehog Signaling pathway Involved in Neoplasm Formation Using Text-Mining Approach

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Big Data Mining and Analytics 2024年第1期7卷 107-130页

作者： Nadezhda Yu.Biziukova Sergey M.Ivanov Oga A.Tarasova Department of Bioinformatics Institute of Biomedical ChemistryMoscow 119121Russia Department of Bioinformatics Pirogov Russian National Research Medical UniversityMoscow 117997Russia

Analysis of molecular mechanisms that lead to the development of various types of tumors is essential for biology and medicine,because it may help to find new therapeutic opportunities for cancer treatment and cure including personalized treatment approaches.One of the pathways known to be important for the development of neoplastic diseases and pathological processes is the hedgehog signaling pathway that normally controls human embryonic development.Systematic accumulation of various types of biological data,including interactions between proteins,regulation of genes transcription,proteomics,and metabolomics experiments results,allows the application of computational analysis of these big data for identification of key molecular mechanisms of certain diseases and pathologies and promising therapeutic targets.The aim of this study is to develop a computational approach for revealing associations between human proteins and genes interacting with the hedgehog pathway components,as well as for identifying their roles in the development of various types of tumors.We automatically collect sets of abstract texts from the NCBI PubMed bibliographic database.For recognition of the hedgehog pathway proteins and genes and neoplastic diseases we use a dictionary-based named entity recognition approach,while for all other proteins and genes machine learning method is used.For association extraction,we develop a set of semantic rules.We complete the results of the text analysis with the gene set enrichment analysis.The identified key pathways that may influence the hedgehog pathway and their roles in tumor development are then verified using the information in the literature.

关键词： text-mining data mining hedgehog pathway neoplastic processes enrichment analysis pathology molecularmechanisms

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hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer

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药学学报:英文版 2023年第6期13卷 2601-2612页

作者： Xiaomin Wang Jun Xu Yiming Sun Siyuwei Cao Hanlin Zeng Nan Jin Matthew Shou Shuai Tang Yi Chen Min Huang Cancer Research Center State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Division of Diabetes Endocrinology and MetabolismDepartment of Molecular Physiology and BiophysicsVanderbilt University Medical CenterNashvilleTN 37232USA

Epigenetic therapies that cause genome-wide epigenetic alterations,could trigger local interplay between different histone marks,leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment.However,in human cancers with diverse oncogenic activation,how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood.We herein discover that the hedgehog(Hh)pathway reprograms the histone methylation landscape in breast cancer,especially in triple-negative breast cancer(TNBC).This facilitates the histone acetylation caused by histone deacetylase(HDAC)inhibitors and gives rise to new therapeutic vulnerability of combination therapies.Specifically,overexpression of zinc finger protein of the cerebellum 1(ZIC1)in breast cancer promotes Hh activation,facilitating the switch of H3K27 methylation(H3K27me)to acetylation(H3K27ac).The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes.Using multiple in vivo breast cancer models including patient-derived TNBC xenograft,we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer.Together,this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

关键词： HDAC inhibitors Drug resistance Histone methylation Histone acetylation Epigenetic interplay hedgehog pathway ZIC1 LIFR Combination therapy Breast cancer

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Where are the theca cells from: the mechanism of theca cells derivation and differentiation

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Chinese Medical Journal 2020年第14期133卷 1711-1718页

作者： Tao Liu Qing-Yuan Qin Jiang-Xue Qu Hai-Yan Wang Jie Yan Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China Key Laboratory of Assisted Reproduction Ministry of EducationBeijing 100191China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction Beijing 100191China

Mammalian follicles are composed of oocytes,granulosa cells,and theca cells.Theca cells form in the secondary follicles,maintaining follicular structural integrity and secreting steroid hormones.Two main sources of theca cells exist:Wilms tumor 1 positive(Wt1+)cells native to the ovary and Gli1+mesenchymal cells migrated from the mesonephros.Normal folliculogenesis is a process where oocytes,granulosa cells,and theca cells constantly interact with and support each other through autocrine and paracrine mechanisms.The proliferation and differentiation of theca cells are regulated by oocyte-derived factors,including growth development factor 9 and bone morphogenetic protein 15,and granulosa cell-derived factors,including desert hedgehog,Indian hedgehog,kit ligand,insulin-like growth factor 1,as well as hormones such as insulin and growth hormones.Current research on the origin of theca cells is limited.Identifying the origin of theca cells will help us to systematically elaborate the mechanisms of follicular formation and development.

关键词： Theca cell hedgehog pathway Growth development factor 9 Bone morphogenetic protein 15 TGF-b superfamily Kit ligand

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