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| 1 | Wnt/b-catenin signaling plays an ever-expanding role in stem cell self-renewal,tumorigenesis and cancer chemoresistance显示文摘Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance. | Maryam K.Mohammed Connie Shao Jing Wang Qiang Wei Xin Wang Zachary Collier Shengli Tang Hao Liu Fugui Zhang Jiayi Huang Dan Guo Minpeng Lu Feng Liu Jianxiang Liu Chao Ma Lewis L.Shi Aravind Athiviraham Tong-Chuan He Michael J.Lee | 2016 | Genes & Diseases2016，3，1： | 70 |
| 2 | Resveratrol provides neuroprotection by regulating the JAK2/STAT3/PI3K/AKT/mTOR pathway after stroke in rats显示文摘Ischemic stroke is a common disease with high mortality and morbidity worldwide.One of the important pathophysiological effects of ischemic stroke is apoptosis.A neuroprotective effect is defined as the inhibition of neuronal apoptosis to rescue or delay the infarction in the surviving ischemic penumbra.Resveratrol is a natural polyphenol that reportedly prevents cerebral ischemia injury by regulating the expression of PI3K/AKT/mTOR.Therefore,this study aimed to elucidate the neuroprotective effect of resveratrol on cerebral ischemia/reperfusion injury and to investigate the signaling pathways and mechanisms through which resveratrol regulates apoptosis in the ischemic penumbra.Rats were subjected to middle cerebral artery occlusion for 2 h followed by 24 h reperfusion.Cerebral infarct volume was measured using 2%TTC staining.TUNEL staining was conducted to evaluate neuronal apoptosis.Western blotting and immunohistochemistry were used to detect the proteins involved in the JAK2/STAT3/PI3K/AKT/mTOR pathway.The results suggested that resveratrol significantly improved neurological function,reduced cerebral infarct volume,decreased neuronal damage,and markedly attenuated neuronal apoptosis;these effects were attenuated by the inhibition of PI3K/AKT with LY294002 and JAK2/STAT3 with AG490.We also found that resveratrol significantly upregulated the expression of p-JAK2,p-STAT3,p-AKT,p-mTOR,and BCL-2 and downregulated expression of cleaved caspase-3 and BAX,which was partially reversed by LY294002 and AG490.These results suggested that resveratrol provides a neuroprotective effect against cerebral ischemia/reperfusion injury,which is partially mediated by the activation of JAK2/STAT3 and PI3K/AKT/mTOR.Resveratrol may indirectly upregulate the PI3K/AKT/mTOR pathway by activating JAK2/STAT3. | Yongying Hou Ke Wang Weijun Wan Yue Cheng Xia Pu Xiufeng Ye | 2018 | Genes & Diseases2018，5，3： | 60 |
| 3 | Bone Morphogenetic Protein (BMP) signaling in development and human diseases显示文摘Bone Morphogenetic Proteins(BMPs)are a group of signaling molecules that belongs to the Transforming Growth Factor-b(TGF-b)superfamily of proteins.Initially discovered for their ability to induce bone formation,BMPs are now known to play crucial roles in all organ systems.BMPs are important in embryogenesis and development,and also in maintenance of adult tissue homeostasis.Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects,highlighting the essential functions of BMPs.In this review,we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development.A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling. | Richard N.Wang Jordan Green Zhongliang Wang Youlin Deng Min Qiao Michael Peabody Qian Zhang Jixing Ye Zhengjian Yan Sahitya Denduluri Olumuyiwa Idowu Melissa Li Christine Shen Alan Hu Rex C.Haydon Richard Kang James Mok Michael J.Lee Hue L.Luu Lewis L.Shi | 2014 | Genes & Diseases2014，1，1： | 47 |
| 4 | Advances in the early diagnosis of hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC)is one of the most prevalent cancers globally.In contrast to the declining death rates observed for all other common cancers such as breast,lung,and prostate cancers,the death rates for HCC continue to increase by^2e3%per year because HCC is frequently diagnosed late and there is no curative therapy for an advanced HCC.The early diagnosis of HCC is truly a big challenge.Over the past years,the early diagnosis of HCC has relied on surveillance with ultrasonography(US)and serological assessments of alpha-fetoprotein(AFP).However,the specificity and sensitivity of US/AFP is not satisfactory enough to detect early onset HCC.Recent technological advancements offer hope for early HCC diagnosis.Herein,we review the progress made in HCC diagnostics,with a focus on emerging imaging techniques and biomarkers for early disease diagnosis. | Weiyi Wang Chao Wei | 2020 | Genes & Diseases2020，7，3： | 42 |
| 5 | Urine-derived stem cells:A novel and versatile progenitor source for cell-based therapy and regenerative medicine显示文摘Engineered functional organs or tissues,created with autologous somatic cells and seeded on biodegradable or hydrogel scaffolds,have been developed for use in individualswith tissue damage suffered fromcongenital disorders,infection,irradiation,or cancer.However,in those patients,abnormal cells obtained by biopsy fromthe compromised tissue could potentially contaminate the engineered tissues.Thus,an alternative cell source for construction of the neo-organ or functional recovery of the injured or diseased tissues would be useful.Recently,we have found stem cells existing in the urine.These cells are highly expandable,and have self-renewal capacity,paracrine properties,and multi-differentiation potential.As a novel cell source,urine-derived stem cells(USCs)provide advantages for cell therapy and tissue engineering applications in regeneration of various tissues,particularly in the genitourinary tract,because they originate from the urinary tract system.Importantly,USCs can be obtained via a non-invasive,simple,and low-cost approach and induced with high efficiency to differentiate into three dermal cell lineages. | Deying Zhang Guanghui Wei Peng Li Xiaobo Zhou Yuanyuan Zhang | 2014 | Genes & Diseases2014，1，1： | 34 |
| 6 | Temozolomide resistance in glioblastoma multiforme显示文摘Temozolomide(TMZ)is an oral alkylating agent used to treat glioblastoma multiforme(GBM)and astrocytomas.However,at least 50%of TMZ treated patients do not respond to TMZ.This is due primarily to the over-expression of O6-methylguanine methyltransferase(MGMT)and/or lack of a DNA repair pathway in GBM cells.Multiple GBM cell lines are known to contain TMZ resistant cells and several acquired TMZ resistant GBM cell lines have been developed for use in experiments designed to define the mechanism of TMZ resistance and the testing of potential therapeutics.However,the characteristics of intrinsic and adaptive TMZ resistant GBM cells have not been systemically compared.This article reviews the characteristics and mechanisms of TMZ resistance in natural and adapted TMZ resistant GBM cell lines.It also summarizes potential treatment options for TMZ resistant GBMs. | Sang Y.Lee | 2016 | Genes & Diseases2016，3，3： | 26 |
| 7 | Breast cancer development and progression:Risk factors,cancer stem cells,signaling pathways,genomics,and molecular pathogenesis显示文摘As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast.While the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this malignancy.Breast cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in between.Within the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites.It is important to distinguish between the various subtypes because they have different prognoses and treatment implications.As there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem cells.Normal breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell motility.Furthermore,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast cancer.This review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer. | Yixiao Feng Mia Spezia Shifeng Huang Chengfu Yuan Zongyue Zeng Linghuan Zhang Xiaojuan Ji Wei Liu Bo Huang Wenping Luo Bo Liu Yan Lei Scott Du Akhila Vuppalapati Hue H.Luu Rex C.Haydon Tong-Chuan He Guosheng Ren | 2018 | Genes & Diseases2018，5，2： | 24 |
| 8 | Insulin-like growth factor(IGF)signaling in tumorigenesis and the development of cancer drug resistance显示文摘One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors.Despite recent advances in diagnostic practices and surgical interventions,many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy.As a result,the prognosis for many patients afflicted with these aggressive cancers remains bleak.The insulin-like growth factor(IGF)signaling axis has been shown to play critical role in the development and progression of various tumors.Many basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various malignancies.There also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care therapy.By better understanding both the IGF-dependent and-independent mechanisms by which pathway members can influence drug sensitivity,we can eventually aim to use modulators of IGF signaling to augment the effects of current therapy.This review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug resistance.We offer a brief overview of IGF signaling and its general role in neoplasia,and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to therapy.Ultimately,our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance. | Sahitya K.Denduluri Olumuyiwa Idowu Zhongliang Wang Zhan Liao Zhengjian Yan Maryam K.Mohammed Jixing Ye Qiang Wei Jing Wang Lianggong Zhao Hue H.Luu | 2015 | Genes & Diseases2015，2，1： | 21 |
| 9 | Targeting angiogenesis for liver cancer: Past, present, and future显示文摘Liver cancer,mostly hepatocellular carcinoma(HCC),is the second leading cause of cancer mortality globally.Most patients were diagnosed at an advanced stage,and systemic therapy is the standard of care.All the approved systemic therapies for HCC are molecular targeted therapies with anti-angiogenic effects targeting the vascular endothelial growth factor signaling pathway.Sorafenib and lenvatinib are the first-line treatment,and regorafenib,ramucirumab,and cabozantinib are second-line treatment options.Although anti-PD-1 antibodies,including nivolumab and pembrolizumab,demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials,both failed in phase III studies.Anti-angiogenic treatment remains the backbone of systemic therapy for HCC.In this review,we summarized the approved anti-angiogenic medicines and discussed the potential strategies to improve the efficacy of anti-angiogenic therapy,including combination therapy with other treatments,and discussed the approaches to overcome the drawbacks of anti-angiogenic therapies. | Xiao-Dong Zhu Zhao-You Tang Hui-Chuan Sun | 2020 | Genes & Diseases2020，7，3： | 20 |
| 10 | Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit;a critical review显示文摘The emergence of antibiotic resistant bacteria in the healthcare is a serious concern.In the Healthcare premises precisely intensive care unit are major sources of microbial diversity.Recent findings have demonstrated not only microbial diversity but also drug resistant microbes largely habitat in ICU.Pseudomonas aeruginosa found as a part of normal intestinal flora and a significant pathogen responsible for wide range of ICU acquired infection in critically ill patients.Nosocomial infection associated with this organism including gastrointestinal infection,urinary tract infections and blood stream infection.Infection caused by this organism are difficult to treat because of the presence of its innate resistance to many antibiotics(b-lactam and penem group of antibiotics),and its ability to acquire further resistance mechanism to multiple class of antibiotics,including Beta-lactams,aminoglycosides and fluoroquinolones.In the molecular evolution microbes adopted several mechanism to maintain genomic plasticity.The tool microbe use for its survival is mainly biofilm formation,quorum sensing,and horizontal gene transfer and enzyme promiscuity.Such genomic plasticity provide an ideal habitat to grow and survive in hearse environment mainly antibiotics pressure.This review focus on infection caused by Pseudomonas aeruginosa,its mechanisms of resistance and available treatment options.The present study provides a systemic review on major source of Pseudomonas aeruginosa in ICU.Further,study also emphasizes virulence gene/s associated with Pseudomonas aeruginosa genome for extended drug resistance.Study gives detailed overview of antibiotic drug resistance mechanism. | Preeti Pachori Ragini Gothalwal Puneet Gandhi | 2019 | Genes & Diseases2019，6，2： | 20 |
| 11 | Adenovirus-mediated gene delivery:Potential applications for gene and cell-based therapies in the new era of personalized medicine显示文摘With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology,it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies.Despite numerous setbacks,efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases.It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies.There has been a long-lasting interest in using viral vectors,especially adenoviral vectors,to deliver therapeutic genes for the past two decades.Among all currently available viral vectors,adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types.The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development.In fact,among over 2000 gene therapy clinical trials approved worldwide since 1989,a significant portion of the trials have utilized adenoviral vectors.This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors,including adenoviral biology,approaches to engineering adenoviral vectors,and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment,vaccination and regenerative medicine.Current challenges and future directions regarding the use of adenoviral vectors are also discussed.It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine. | Cody S.Lee Elliot S.Bishop Ruyi Zhang Xinyi Yu Evan M.Farina Shujuan Yan Chen Zhao Zongyue Zeng Yi Shu Xingye Wu Jiayan Lei Yasha Li Wenwen Zhang Chao Yang Ke Wu Ying Wu Sherwin Ho Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Russell R.Reid Tong-Chuan He | 2017 | Genes & Diseases2017，4，2： | 19 |
| 12 | Targeting matrix metalloproteinases in cancer:Bringing new life to old ideas显示文摘Since the identification of matrix metalloproteinases(MMPs),a family of zincdependent endopeptidases,as being a driving factor for cancer progression and patient prognosis,MMPs have been studied extensively.Although early programs targeting MMPs were largely unsuccessful in clinical trials,they remain a viable and highly desirable therapeutic target based on preclinical studies and their role in disease progression.As information regarding the structure and function of these proteinases is compiled and biotechnology evolves,tools to develop better inhibitors are within our grasp.Improved methods for high throughput screening and in silico drug design programs have identified compounds which are highly potent,have high binding affinities,and exhibit favorable pharmacokinetic profiles.More recently,advances in drug delivery methods or compounds which bind outside the active site have brought new light to the field.In this review,we highlight the role of MMPs in cancer,clinical trials for MMP inhibitors,and novel approaches to targeting MMPs in cancer. | Jillian Cathcart Ashleigh Pulkoski-Gross Jian Cao | 2015 | Genes & Diseases2015，2，1： | 18 |
| 13 | Age-related macular degeneration: Epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy显示文摘Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of incurable blindness worldwide in the elderly. Clinically, AMD initially affects the central area of retina known as the macula and it is classified as early stage to late stage (advanced AMD). The advanced AMD is classified into the nonexudative or atrophic form (dry AMD) and the exudative or neovascular form (wet AMD). More severe vision loss is typically associated with the wet form. Multiple genetic factors, lipid metabolism, oxidative stress and aging, play a role in the etiology of AMD. Dysregulation in genetic to AMD is established to 46%–71% of disease contribution, with CFH and ARMS2/HTRA1 to be the two most notable risk loci among the 103 identified AMD associated loci so far. Chronic cigarette smoking is the most proven consistently risk living habits for AMD. Deep learning algorithm has been developed based on image recognition to distinguish wet AMD and normal macula with high accuracy. Currently, anti-vascular endothelial growth factor (VEGF) therapy is highly effective at treating wet AMD. Several new generation AMD drugs and iPSC-derived RPE cell therapy are in the clinical trial stage and are promising to improve AMD treatment in the near future. | Yanhui Deng Lifeng Qiao Mingyan Du Chao Qu Ling Wan Jie Li Lulin Huang | 2022 | Genes & Diseases2022，9，1： | 17 |
| 14 | Exploring gut microbes in human health and disease:Pushing the envelope显示文摘Humans have coevolved with their microbes over thousands of years,but this relationship,is now being dramatically affected by shifts in the collective human microbiome resulting from changes in the environment and societal norms.Resulting perturbations of intestinal host-microbe interactions can lead to miscues and altered host responses that increase the risk of pathogenic processes and promote“western”disorders such as inflammatory bowel diseases,cancers,obesity,diabetes,autism,and asthma.Given the current challenges and limitations in gene therapy,approaches that can reshape the gut microbiome represent a reasonable strategy for restoring the balance between host and microbes.In this review and commentary,we highlight recent progress in our understanding of the intestinal microbiome in the context of health and diseases,focusing on mechanistic concepts that underlie the complex relationships between host and microbes.Despite these gains,many challenges lie ahead that make it difficult to close the gap between the basic sciences and clinical application.We will discuss the potential therapeutic strategies that can be used to manipulate the gut microbiota,recognizing that the promise of pharmabiotics(“bugs to drugs”)is unlikely to be completely fulfilled without a greater understanding of enteric microbiota and its impact on mammalian physiology.By leveraging the knowledge gained through these studies,we will be prepared to enter the era of personalized medicine where clinical inventions can be custom-tailored to individual patients to achieve better outcomes. | Jun Sun Eugene B.Chang | 2014 | Genes & Diseases2014，1，2： | 17 |
| 15 | Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC)is one of the common lethal types of tumor all over the world.The lethality of HCC accounts for many reasons.One of them,the lack of reliable diagnostic markers at the early stage,in this context,serum miRNAs became promising diagnostic biomarkers.Herein,we aimed to identify the predictive value of two miRNAs(miR-122 and miR-224)in plasma of patients with HCC preceded by chronic HCV infection.Taqman miRNA assays specific for hsa-miR-122 and hsa-miR-224 were used to assess the expression levels of the chosen miRNAs in plasma samples collected from three groups;40 patients with HCC related to HCV,40 with CHC patients and 20 healthy volunteers.This study revealed that the mean plasma values of miRNA-122 were significantly lower among HCC group when compared to CHC and control groups(P<0.001).Whereas,miR-224 mean plasma values were significantly higher among HCC group when compared to both CHC group and control group.Moreover,it was found that miR-122 can predict development of HCC at cut-off value<0.67(RQ)and(AUC Z 0.98,P<0.001).As regards miR-224,it can predict development of HCC at cut-off value>1.2(RQ)and(AUC Z 0.93,P<0.001),while the accuracy of AFP to diagnose HCC was(AUC:0.619;P Z 0.06).In conclusion,the expression plasma of miR-122 and miR-224 could be used as noninvasive biomarkers for the early prediction of developing HCC at the early stage. | Khalda S.Amr Hanan Abd Elmawgoud Atia Rehab Abd Elazeem Elbnhawy Wafaa M.Ezzat | 2017 | Genes & Diseases2017，4，4： | 17 |
| 16 | Wnt and BMP signaling crosstalk in regulating dental stem cells:Implications in dental tissue engineering显示文摘Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of life.Regenerative dentistry holds great promise in treating oral/dental disorders.The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and differentiation.In this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from gingiva.We then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these pathways.Lastly,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways.We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications.Thus,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade. | Fugui Zhang Jinlin Song Hongmei Zhang Enyi Huang Dongzhe Song Viktor Tollemar Jing Wang Jinhua Wang Maryam Mohammed Qiang Wei Jiaming Fan Junyi Liao Yulong Zou Feng Liu Xue Hu Xiangyang Qu Liqun Chen Xinyi Yu Hue H.Luu Michael J.Lee Tong-Chuan He Ping Ji | 2016 | Genes & Diseases2016，3，4： | 16 |
| 17 | Gut microbiota,inflammation and colorectal cancer显示文摘Although genes contribute to colorectal cancer,the gut microbiota are an important player.Accumulating evidence suggests that chronic infection and the ensuing inflammation contributes to tumor initiation and tumor progression.A variety of bacterial species and tumor-promoting virulence mechanisms have been investigated.Significant advances have been made in understanding the composition and functional capabilities of the gut microbiota and its roles in cancer.In the current review,we discuss the novel roles of microbiota in the progression of colon cancer.Although microbiota technically include organisms other than bacteria e.g.,viruses and fungi,this review will primarily focus on bacteria.We summarize epidemiological studies of human microbiome and colon cancer.We discuss the progress in the scientific understanding of the interplay between the gut microbiota,barrier function,and host responses in experimental models.Further,we discuss the potential application in prevention,diagnosis,and therapy of colon cancer by targeting microbiota.We discuss the challenges lie ahead and the future direction in studying gut microbiome in colon cancer to close the gap between the basic sciences and clinical application. | Jun Sun Ikuko Kato | 2016 | Genes & Diseases2016，3，2： | 16 |
| 18 | The versatile functions of Sox9 in development,stem cells,and human diseases显示文摘The transcription factor Sox9 was first discovered in patients with campomelic dysplasia,a haploinsufficiency disorder with skeletal deformities caused by dysregulation of Sox9 expression during chondrogenesis.Since then,its role as a cell fate determiner during embryonic development has been well characterized;Sox9 expression differentiates cells derived from all three germ layers into a large variety of specialized tissues and organs.However,recent data has shown that ectoderm-and endoderm-derived tissues continue to express Sox9 in mature organs and stem cell pools,suggesting its role in cell maintenance and specification during adult life.The versatility of Sox9 may be explained by a combination of posttranscriptional modifications,binding partners,and the tissue type in which it is expressed.Considering its importance during both development and adult life,it follows that dysregulation of Sox9 has been implicated in various congenital and acquired diseases,including fibrosis and cancer.This review provides a summary of the various roles of Sox9 in cell fate specification,stem cell biology,and related human diseases.Ultimately,understanding the mechanisms that regulate Sox9 will be crucial for developing effective therapies to treat disease caused by stem cell dysregulation or even reverse organ damage. | Alice Jo Sahitya Denduluri Bosi Zhang Zhongliang Wang Liangjun Yin Zhengjian Yan Richard Kang Lewis L.Shi James Mok Michael J.Lee Rex C.Haydon | 2014 | Genes & Diseases2014，1，2： | 16 |
| 19 | Emerging roles of lncRNAs in the post-transcriptional regulation in cancer显示文摘Accumulating evidence indicates that long non-coding RNAs(lncRNAs)can play a pivotal role in regulation of diverse cellular processes.In particular,lncRNAs can serve as master gene regulators at transcriptional and posttranscriptional levels,leading to tumorigenesis.In this review,we discuss latest developments in lncRNA-meditated gene expression at the post-transcriptional level,including gene splicing,mRNA stability,protein stability and nuclear trafficking. | Rong-Zhang He Di-Xian Luo Yin-Yuan Mo | 2019 | Genes & Diseases2019，6，1： | 16 |
| 20 | Bmi-1:At the crossroads of physiological and pathological biology显示文摘Bmi-1 is a member of the Polycomb repressor complex 1 that mediates gene silencing by regulating chromatin structure and is indispensable for self-renewal of both normal and cancer stem cells.Despite three decades of research that have elucidated the transcriptional regulation,post-translational modifications and functions of Bmi-1 in regulating the DNA damage response,cellular bioenergetics,and pathologies,the entire potential of a protein with such varied functions remains to be realized.This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on its role in both normal physiology and cancer.Additionally,since cancer stem cells are emerging as a new paradigm for therapy resistance,the role of Bmi-1 in this perspective is also highlighted.The wide spectrum of malignancies that implicate Bmi-1 as a signature for stemness and oncogenesis also make it a suitable candidate for therapy.Nonetheless,new approaches are vitally needed to further characterize physiological roles of Bmi-1 with the long-term goal of using Bmi-1 as a prognostic marker and a therapeutic target. | Resham Bhattacharya Soumyajit Banerjee Mustafi Mark Street Anindya Dey Shailendra Kumar Dhar Dwivedi | 2015 | Genes & Diseases2015，2，3： | 15 |
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