Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to deg...Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.展开更多
Androgen and androgen receptor （AR） play important roles in male spermatogenesis and fertility, yet detailed androgen/AR signals in Sertoli cells remain unclear. To identify AR target genes in Sertoli cells, we anal...Androgen and androgen receptor （AR） play important roles in male spermatogenesis and fertility, yet detailed androgen/AR signals in Sertoli cells remain unclear. To identify AR target genes in Sertoli cells, we analyzed the gene expression profiles of testis between mice lacking AR in Sertoli cells （S-AR-/y） and their littermate wild-type （WT） mice. Digital gene expression analysis identified 2276 genes downregulated and 2865 genes upregulated in the S-AR-/y mice testis compared to WT ones. To further nail down the difference within Sertoli cells, we first constructed Sertoli cell line TM4 with stably transfected AR （named as TM4/AR） and found androgens failed to transactivate AR in Sertoli TM4 and TM4/AR cells. Interestingly, additional transient transfection of AR-cDNA resulted in significant androgen responsiveness with TM4/AR cells showing 10 times more androgen sensitivity than TM4 cells. In the condition where maximal androgen response was demonstrated, we then analyzed gene expression and found the expression levels of 2313 genes were changed more than twofold by transient transfection of AR-cDNA in the presence of testosterone. Among these genes, 603 androgen-/ AR-regulated genes, including 164 upregulated and 439 downregulated, were found in both S-AR-/y mice testis and TM4/AR cells. Using informatics analysis, the gene ontology was applied to analyze these androgen-/AR-regulated genes to predict the potential roles of androgen/AR in the process of spermatogenesis. Together, using gene analysis in both S-AR-/y mice testis and TM4/AR cells may help us to better understand the androeen/AR signals in Sertoli cells and their influences in spermatogenesis.展开更多
Objective： The aim of the study was to investigate the association of esophageal squamous cell carcinoma （ESCC） genetic susceptibility with the single nucleotide polymorphism （SNP） rs679620 （-Lys45Glu-） in exon...Objective： The aim of the study was to investigate the association of esophageal squamous cell carcinoma （ESCC） genetic susceptibility with the single nucleotide polymorphism （SNP） rs679620 （-Lys45Glu-） in exon 2 of the romp3 gene, and the population in high incidence region of Henan （China） was selected for exploring the mechanism by case-control study, Methods： The romp3 SNP was genotyped by PCR-RFLP analysis in total 605 cases of Henan population, in which there were 227 ESCC cases and 197 controls of An-yang in Henan plus 181 controls of emigrants in Hubei from Xi-chuan of Henan, China. Results： The statistic data showed that GIG and G/A genotype frequencies of SNP rs679620 were significantly different between the controls of emigrants of Xi-chuan in Hubei and controls of An-yang in Henan （P 〈 0.01） also the ESCC cases of An-yang in Henan （P 〈 0.01）, respectively. Conclusion： This study suggests that the SNP rs679620 （-Lys45Glu-） in exon 2 of the mmp3 gene might be associated with ESCC genetic susceptibility.展开更多
Testicular nuclear receptor 4(TR4),also known as NR2C2(nuclear receptor subfamily 2,group C,member 2),is a transcriptional factor and a member of the nuclear receptor family.TR4 was initially cloned from human and rat...Testicular nuclear receptor 4(TR4),also known as NR2C2(nuclear receptor subfamily 2,group C,member 2),is a transcriptional factor and a member of the nuclear receptor family.TR4 was initially cloned from human and rat hypothalamus,prostate,and testes libraries.For almost two decades,its specific tissue distribution,genomic organization,and chromosomal assignment have been well investigated in humans and animals.However,it has been very difficult to study TR4's physiological functions due to a lack of specific ligands.Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4.In vivo studies of TR4 gene knockout mice(TR4-/-) found that they display severe spinal curvature,subfertility,premature aging,and prostate prostatic intraepithelial neoplasia(PIN) development.Upstream modulators,downstream target gene regulation,feedback mechanisms,and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been identified in studies using the TR4-/-phenotype.With the establishment of a tissue-specific TR4-/-mouse model,research on TR4 will be more convenient in the future.展开更多
Androgen deprivation therapy （ADT）, which aims to reduce androgen-androgen receptor （AR） signaling, is the normal method of prostate cancer treatment. Despite its early success in suppressing prostate tumor growth...Androgen deprivation therapy （ADT）, which aims to reduce androgen-androgen receptor （AR） signaling, is the normal method of prostate cancer treatment. Despite its early success in suppressing prostate tumor growth, the therapy eventually fails, leading to recurrent hormone-refractory tumor growth. Recent studies have been carried out with stromal cell-specific or fibroblastspecific AR knockout mice or prostate stromal-specific and epithelial-specific AR knockout transgenic mice prostate cancer models and in vitro and in vivo studies of various human prostate cancer cells with knock-in and knock-out of the AR. These have indicated that the AR in prostatic stroma acts as a proliferation stimulator and survival factor, whereas epithelial AR acts as a survival factor for epithelial luminal cells and stromal smooth muscle cell differentiation, and as a suppressor for epithelial basal intermediate cell proliferation. These two opposite AR pose a major challenge for roles of the stromal and epithelial ADT and should be taken into account when developing new therapies targeting AR in selective cells.展开更多
Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only ...Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only a small subset of late-stage HCC patients responds positively to recently developed therapeutic innovations.MicroRNAs (miRNAs) act as an ancillary epigenetic system that can regulate genome expression in all cancerpathways including HCC. The molecular mechanisms of miRNA regulation in cancer pathogenesis offered researchersa new approach that was widely hoped would translate into miRNA-based drugs and diagnostics. Thirty years on,miRNA-based diagnostic and therapeutic agents for HCC remain a work-in-progress (WIP) and no current miRNAHCC clinical trial has progressed to Phase 4. The question remains why this is the case after 30 years and what is theway forward. The major findings and contribution of this paper are that it illustrates the complexity of the HBVmiRNA interactome in HBV-HCC in all cellular processes, as well as the ancillary role of miRNA in the epigeneticand immune systems. This is combined with a review of the outcomes and problems of clinical trials, to explain whymiRNA therapeutics and diagnostics have not progressed to approved drugs or serum-based diagnostic tests. The wayforward suggests a radical rethink might be so that involves the incorporation of AI, bioinformatics, andnanotechnology to solve the problem.展开更多
In this article,there were errors in the images presented in Figure 3Ab(bottom left)and Figure 5D(2nd and 4th columns).These were caused by miss-insertion of the images during preparation of the manuscript for submiss...In this article,there were errors in the images presented in Figure 3Ab(bottom left)and Figure 5D(2nd and 4th columns).These were caused by miss-insertion of the images during preparation of the manuscript for submission.Since raw data of the images in Figure 5D were lost,the authors re-performed the whole experiment and provided new similar results(both images and quantitation graphs)for an update.The corrected Figure 3Ab left panel and updated Figure 5D are shown as below.The details have been corrected only in this corrigendum to preserve the published version of record.The authors assure that the original results or conclusions are not altered and they apologize for the mistake.展开更多
基金supported by the National Natural Science Foundation of China(82103298)Basic Research Project of Science and Technology Cooperation in Qiandongnan Prefecture(No.2023-16).
文摘Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.
基金This work was supported by the National Natural Science Foundation of China （no. 30971636）, and the George H. Whipple Professorship Endowment, and National Science Council, Talwan, China （96-2314-B-182A-023-MY2 and 97- 2314-B-182A-077-MY3）. Supplementary Information accompanies the paper on Asian lournal of Andrology website （http：Hwww.nature.com/aja）.
文摘Androgen and androgen receptor （AR） play important roles in male spermatogenesis and fertility, yet detailed androgen/AR signals in Sertoli cells remain unclear. To identify AR target genes in Sertoli cells, we analyzed the gene expression profiles of testis between mice lacking AR in Sertoli cells （S-AR-/y） and their littermate wild-type （WT） mice. Digital gene expression analysis identified 2276 genes downregulated and 2865 genes upregulated in the S-AR-/y mice testis compared to WT ones. To further nail down the difference within Sertoli cells, we first constructed Sertoli cell line TM4 with stably transfected AR （named as TM4/AR） and found androgens failed to transactivate AR in Sertoli TM4 and TM4/AR cells. Interestingly, additional transient transfection of AR-cDNA resulted in significant androgen responsiveness with TM4/AR cells showing 10 times more androgen sensitivity than TM4 cells. In the condition where maximal androgen response was demonstrated, we then analyzed gene expression and found the expression levels of 2313 genes were changed more than twofold by transient transfection of AR-cDNA in the presence of testosterone. Among these genes, 603 androgen-/ AR-regulated genes, including 164 upregulated and 439 downregulated, were found in both S-AR-/y mice testis and TM4/AR cells. Using informatics analysis, the gene ontology was applied to analyze these androgen-/AR-regulated genes to predict the potential roles of androgen/AR in the process of spermatogenesis. Together, using gene analysis in both S-AR-/y mice testis and TM4/AR cells may help us to better understand the androeen/AR signals in Sertoli cells and their influences in spermatogenesis.
基金Supported by a grant from the Natural Sciences Foundation of State Ethnic Affairs Commission of China (No. 07ZN09)
文摘Objective： The aim of the study was to investigate the association of esophageal squamous cell carcinoma （ESCC） genetic susceptibility with the single nucleotide polymorphism （SNP） rs679620 （-Lys45Glu-） in exon 2 of the romp3 gene, and the population in high incidence region of Henan （China） was selected for exploring the mechanism by case-control study, Methods： The romp3 SNP was genotyped by PCR-RFLP analysis in total 605 cases of Henan population, in which there were 227 ESCC cases and 197 controls of An-yang in Henan plus 181 controls of emigrants in Hubei from Xi-chuan of Henan, China. Results： The statistic data showed that GIG and G/A genotype frequencies of SNP rs679620 were significantly different between the controls of emigrants of Xi-chuan in Hubei and controls of An-yang in Henan （P 〈 0.01） also the ESCC cases of An-yang in Henan （P 〈 0.01）, respectively. Conclusion： This study suggests that the SNP rs679620 （-Lys45Glu-） in exon 2 of the mmp3 gene might be associated with ESCC genetic susceptibility.
基金supported by the National Natural Science Foundation of China (No.30973001)the National Basic Research Program (973) of China (No.2012CB518304)+2 种基金the Zhejiang Provincial Natural Science Foundation of China (No.Y2110446)the Qianjiang Talents Project of Zhejiang Province (No.2011R10039)the PAO Yu-kong International Foundation for Scholars and Scientists,China
文摘Testicular nuclear receptor 4(TR4),also known as NR2C2(nuclear receptor subfamily 2,group C,member 2),is a transcriptional factor and a member of the nuclear receptor family.TR4 was initially cloned from human and rat hypothalamus,prostate,and testes libraries.For almost two decades,its specific tissue distribution,genomic organization,and chromosomal assignment have been well investigated in humans and animals.However,it has been very difficult to study TR4's physiological functions due to a lack of specific ligands.Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4.In vivo studies of TR4 gene knockout mice(TR4-/-) found that they display severe spinal curvature,subfertility,premature aging,and prostate prostatic intraepithelial neoplasia(PIN) development.Upstream modulators,downstream target gene regulation,feedback mechanisms,and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been identified in studies using the TR4-/-phenotype.With the establishment of a tissue-specific TR4-/-mouse model,research on TR4 will be more convenient in the future.
文摘Androgen deprivation therapy （ADT）, which aims to reduce androgen-androgen receptor （AR） signaling, is the normal method of prostate cancer treatment. Despite its early success in suppressing prostate tumor growth, the therapy eventually fails, leading to recurrent hormone-refractory tumor growth. Recent studies have been carried out with stromal cell-specific or fibroblastspecific AR knockout mice or prostate stromal-specific and epithelial-specific AR knockout transgenic mice prostate cancer models and in vitro and in vivo studies of various human prostate cancer cells with knock-in and knock-out of the AR. These have indicated that the AR in prostatic stroma acts as a proliferation stimulator and survival factor, whereas epithelial AR acts as a survival factor for epithelial luminal cells and stromal smooth muscle cell differentiation, and as a suppressor for epithelial basal intermediate cell proliferation. These two opposite AR pose a major challenge for roles of the stromal and epithelial ADT and should be taken into account when developing new therapies targeting AR in selective cells.
文摘Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only a small subset of late-stage HCC patients responds positively to recently developed therapeutic innovations.MicroRNAs (miRNAs) act as an ancillary epigenetic system that can regulate genome expression in all cancerpathways including HCC. The molecular mechanisms of miRNA regulation in cancer pathogenesis offered researchersa new approach that was widely hoped would translate into miRNA-based drugs and diagnostics. Thirty years on,miRNA-based diagnostic and therapeutic agents for HCC remain a work-in-progress (WIP) and no current miRNAHCC clinical trial has progressed to Phase 4. The question remains why this is the case after 30 years and what is theway forward. The major findings and contribution of this paper are that it illustrates the complexity of the HBVmiRNA interactome in HBV-HCC in all cellular processes, as well as the ancillary role of miRNA in the epigeneticand immune systems. This is combined with a review of the outcomes and problems of clinical trials, to explain whymiRNA therapeutics and diagnostics have not progressed to approved drugs or serum-based diagnostic tests. The wayforward suggests a radical rethink might be so that involves the incorporation of AI, bioinformatics, andnanotechnology to solve the problem.
文摘In this article,there were errors in the images presented in Figure 3Ab(bottom left)and Figure 5D(2nd and 4th columns).These were caused by miss-insertion of the images during preparation of the manuscript for submission.Since raw data of the images in Figure 5D were lost,the authors re-performed the whole experiment and provided new similar results(both images and quantitation graphs)for an update.The corrected Figure 3Ab left panel and updated Figure 5D are shown as below.The details have been corrected only in this corrigendum to preserve the published version of record.The authors assure that the original results or conclusions are not altered and they apologize for the mistake.
