There are still controversies about the roles of microRNA-26a（miR-26a）in human malignancies,as it is a tumor suppressor in breast cancer,gastric cancer,and hepatocellular carcinoma,but is an oncogene in glioma and c...There are still controversies about the roles of microRNA-26a（miR-26a）in human malignancies,as it is a tumor suppressor in breast cancer,gastric cancer,and hepatocellular carcinoma,but is an oncogene in glioma and cholangiocarcinoma.Until now,the function of miR-26a in osteosarcoma remains largely elusive.Here,we found that miR-26a was downregualted in osteosarcoma tissues.Using in vitro and in vivo assays,we confirmed that miR-26a could inhibit the abilities of in vitro proliferation and suppress in vivo tumor growth in mouse model.Furthermore,we identified insulin-like growth factor 1（IGF-1）as a novel and direct target of miR-26a and revealed that miR-26a exerted its tumor-suppressor function,at least in part,by inhibiting IGF-1expression.These findings contribute to our understanding of the functions of miR-26a in osteosarcoma.展开更多
MicroRNAs(miRNAs) are a class of non-coding RNAs that hybridize to mRNAs and induce either translation repression or mRNA cleavage.Recently,it has been reported that miRNAs could possibly play a critical role in cellu...MicroRNAs(miRNAs) are a class of non-coding RNAs that hybridize to mRNAs and induce either translation repression or mRNA cleavage.Recently,it has been reported that miRNAs could possibly play a critical role in cellular processes like regulation of cell growth,differentiation,and apoptosis,emphasizing their role in tumorigenesis.Likewise,several miRNA's are involved in lung cancer tumorigenesis.The present review puts forth a database of human miRNA's involved in lung cancer along with their target genes.It also provides sequences of miRNA's and their chromosomal locations retrieved from different databases like microCosm(218 microRNAs),PhenomiR(293 microRNAs),and mir2Disease(90 microRNAs) and target gene information such as the pathways like cell cycle regulation,angiogenesis,apoptosis etc.Though miRNA's are still to be explored,they hold a promise as therapeutic targets and diagnostic markers of cancer.展开更多
Parkinson＇s disease（PD） is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain ...Parkinson＇s disease（PD） is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons. Oxidative stress is also recognized as one of the main causes of PD, and excessive reactive oxygen species（ROS） and reactive nitrogen species can lead to dopaminergic neuron vulnerability and eventual death. Micro RNAs control a range of physiological and pathological functions, and may serve as potential targets for intervention against PD to mitigate damage to the brain. Several studies have demonstrated that micro RNAs can regulate oxidative stress and prevent ROS-mediated damage to dopaminergic neurons, suggesting that specific micro RNAs may be putative targets for novel therapeutic strategies in PD. Recent human and animal studies have identified a large number of dysregulated micro RNAs in PD brain tissue samples, many of which were downregulated. The dysregulated micro RNAs affect downstream targets such as SNCA, PARK2, LRRK2, TNFSF13 B, LTA, SLC5 A3, PSMB2, GSR, GBA, LAMP-2 A, HSC. Apart from one study, none of the studies reviewed had used agomirs or antagomirs to reverse the levels of downregulated or upregulated micro RNAs, respectively, in mouse models of PD or with isolated human or mouse dopaminergic cells. Further large-scale studies of brain tissue samples collected with short postmortem interval from human PD patients are warranted to provide more information on the micro RNA profiles in different brain regions and to test for gender differences.展开更多
MicroRNAs (miRNAs) are a class of ~22 nucleotides long non coding RNA molecules which play an important role in gene regulation at the post transcriptional level. The conserved nature of miRNAs provides the basis of n...MicroRNAs (miRNAs) are a class of ~22 nucleotides long non coding RNA molecules which play an important role in gene regulation at the post transcriptional level. The conserved nature of miRNAs provides the basis of new miRNA identification through homology search. In an attempt to identify new conserved miRNAs in tea, previously known plant miRNAs were used for searching their homolog in a tea Expressed Sequence Tags and full length nucleotide sequence database. The sequences showing homolog no more than four mismatches were predicted for their fold back structures and passed through a series of filtration criteria, finally led us to identify 13 conserved miRNAs in tea belonging to 9 miRNA families. A total of 37 potential target genes in Arabidopsis were identified subsequently for 7 miRNA families based on their sequence complementarity which encode transcription factors (8%), enzymes (30%) and transporters (14%) as well as other proteins involved in physiological and metabolic processes (48%). Overall, our findings will accelerate the way for further researches of miRNAs and their functions in tea.展开更多
MicroRNAs （miRNAs） are a class of newly identified, small, non-coding RNAs that play vital roles in regulation. Based on miRNAs unique features of expression pattern, evolutionary conservation, secondary structure a...MicroRNAs （miRNAs） are a class of newly identified, small, non-coding RNAs that play vital roles in regulation. Based on miRNAs unique features of expression pattern, evolutionary conservation, secondary structure and genetic requirements for biogenesis, computational predication strategy is adopted to predicate the novel miRNAs. In this research, potential miRNAs and their targets in grapevine （Vitis vinifera） were predicted. We used previously known plant miRNAs against grapevine genome sequence databases to search for potential miRNAs. A total of 81 potential miRNAs were detected following a range of strict filtering criteria. Using these potential miRNA sequences, we could further blast the mRNA database to find the potential targets in this species. Comparative analysis of miRNAs in grapevine and other species reveals that miRNAs exhibit an evolutional conservation, the number and function of miRNAs must have significantly expanded during the evolution of land plants. Furthermore divergence made versatile functions of miRNAs feasible. Cluster of miRNAs likely represents an ancient expression mechanism. Predicted target genes include not only transcription factors but also genes implicated in floral development, signal transduction, diseases and stress response. Till now, little is known about experimental or computational identification of miRNA in grapevine species. Increased knowledge of the biological mechanisms of the grapevine will allow targeted approaches to increase the quality of fruit and reduce the impact of parasites together with stress, which could enable a sustainable, environmentally-sound, farming policv.展开更多
Traumatic brain injury （TBI） is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that event...Traumatic brain injury （TBI） is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as develop- ment, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma （miR-425-p, -21, -93, -191 and -499） and cerebro-spinal fluid （CSF） （miR-328, -362-3p, -451, -486a） as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TBI （e.g., miR-21, miR-23b）. MicroRNA profil- ing was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TBI （e.g., miR-21） have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in microRNA profiles in different age groups （children, adults, and elderly）.展开更多
Study on shrimp miRNAs was limited and just 7 mature miRNA sequences of Marsupenaeus japonicus are deposited in mir Base database. In this study, miRNAs and their target gene candidates were computationally identified...Study on shrimp miRNAs was limited and just 7 mature miRNA sequences of Marsupenaeus japonicus are deposited in mir Base database. In this study, miRNAs and their target gene candidates were computationally identified from shrimp Penaeu s monodon and then experimentally validated. Using 39 908 expressed sequence tags(ESTs) and 21 124 genome survey sequences(GSSs) of P. monodon(pmo) as reference dataset, a comprehensive approach based on inter-species homolog search was employed to investigate the candidate miRNAs(i.e. pmo-miRNA). A total of eight miRNAs belonging to 7 families were computationally identified and five out of them were subsequently validated by PCR and sequencing. Of these, pmo-miR-4961a, pmo-miR-4961b, pmo-miR-4979 and pmo-miR-3819 were first identified from shrimps. Both the mature pmo-miRNAs and the corresponding precursors were conserved among different species. Based on perfect or near-perfect match to the target region, the target gene candidates of pmomiRNAs were predicted from 10 331 mRNA sequences of P. monodon. A total of 20 genes were predicted as the targets of pmo-miR-4961a, pmo-miR-4961b, pmo-miR-4979 and pmo-miR-6492. Experimental validation by dual luciferase reporter assay confi rmed the targeting between 3 pmo-miRNAs and one or two of their target genes, especially the pmo-miR-4979 which could significantly down-regulate the expression of target gene(JR226772). This study updates the miRNAs and their targets in P. monodon and lays a solid foundation for future RNAi study.展开更多
Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently...Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients(80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are des-perately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC.展开更多
To determine the molecular mechanism of cerebral ischemia/reperfusion injury, we examined the micro RNA（mi RNA） expression profile in rat cortex after focal cerebral ischemia/reperfusion injury using mi RNA microarr...To determine the molecular mechanism of cerebral ischemia/reperfusion injury, we examined the micro RNA（mi RNA） expression profile in rat cortex after focal cerebral ischemia/reperfusion injury using mi RNA microarrays and bioinformatic tools to systematically analyze Gene Ontology（GO） function classifications, as well as the signaling pathways of genes targeted by these differentially expressed mi RNAs. Our results show significantly changed mi RNA expression profiles in the reperfusion period after focal cerebral ischemia, with a total of 15 mi RNAs up-regulated and 44 mi RNAs down-regulated. Target genes of these differentially expressed mi RNAs were mainly involved in metabolic and cellular processes, which were identified as hub nodes of a mi RNA-GO-network. The most correlated pathways included D-glutamine and D-glutamate metabolism, the renin-angiotensin system, peroxisomes, the PPAR signaling pathway, SNARE interactions in vesicular transport, and the calcium signaling pathway. Our study suggests that mi RNAs play an important role in the pathological process of cerebral ischemia/reperfusion injury. Understanding mi RNA expression and function may shed light on the molecular mechanism of cerebral ischemia/reperfusion injury.展开更多
Primary liver cancer is a global disease that is on the increase.Hepatocellular carcinoma(HCC)accounts for most primary liver cancers and has a notably low survival rate,largely attributable to late diagnosis,resistan...Primary liver cancer is a global disease that is on the increase.Hepatocellular carcinoma(HCC)accounts for most primary liver cancers and has a notably low survival rate,largely attributable to late diagnosis,resistance to treatment,tumour recurrence and metastasis.MicroRNAs(miRNAs/miRs)are regulatory RNAs that modulate protein synthesis.miRNAs are involved in several biological and pathological processes including the development and progression of HCC.Given the poor outcomes with current HCC treatments,miRNAs represent an important new target for therapeutic intervention.Several studies have demonstrated their role in HCC development and progression.While many risk factors underlie the development of HCC,one process commonly altered is iron homeostasis.Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised.Aberrant miRNA expression in hepatic fibrosis and injury response have been reported,as have dysregulated miRNA expression patterns affecting cell cycle progression,evasion of apoptosis,invasion and metastasis.In2009,miR-26a delivery was shown to prevent HCC progression,highlighting its therapeutic potential.Several studies have since investigated the clinical potential of other miRNAs with one drug,Miravirsen,currently in phaseⅡclinical trials.miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy.Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years,yielding improved HCC survival rates and patient outcomes.展开更多
Colorectal cancer(CRC) is the third most common cancer in western countries. Despite significant improvement in available treatment options, CRC still remains the second leading cause of cancer-related death. Traditio...Colorectal cancer(CRC) is the third most common cancer in western countries. Despite significant improvement in available treatment options, CRC still remains the second leading cause of cancer-related death. Traditionally, 5-fluorouracil has been used as the main chemotherapy drug for treatment of metastatic CRC(mCRC). However, during the last two decades more effective chemotherapeutic agents such as oxaliplatin, irinotecan and the monoclonal antibodies cetuximab, panitumumab and bevacizumab have been used in clinical practice. More recently, the therapeutic armamentarium has been supplemented by the monoclonal antibodies bevacizumab, cetuximab and panitumumab as well as the protein-trap aflibercept and the smallmolecule multi-kinase inhibitor regorafenib. One of the major problems for the management of CRC is the inherent or acquired resistance to therapeutic approaches. The discovery of microRNAs(miRNAs), a class of small, endogenous, non-coding, single-stranded RNAs that play a role as post-transcriptional regulators, has added new dimensions to the diagnosis and treatment of cancer. Because miRNAs are important regulators of carcinogenesis, progression, invasion, angiogenesis and metastases in CRC, they might serve as potential predictive and prognostic factors and even as therapeutic targets themselves. Several miRNAs are already known to be dysregulated in CRCs and have been linked to biological processes involved in tumor progression and response to anti-cancer therapies. This review summarizes current therapeutic approaches for treating CRC and highlights the role of miRNAs as novel predictive biomarkers and potential drug targets in CRC patients.展开更多
文摘There are still controversies about the roles of microRNA-26a（miR-26a）in human malignancies,as it is a tumor suppressor in breast cancer,gastric cancer,and hepatocellular carcinoma,but is an oncogene in glioma and cholangiocarcinoma.Until now,the function of miR-26a in osteosarcoma remains largely elusive.Here,we found that miR-26a was downregualted in osteosarcoma tissues.Using in vitro and in vivo assays,we confirmed that miR-26a could inhibit the abilities of in vitro proliferation and suppress in vivo tumor growth in mouse model.Furthermore,we identified insulin-like growth factor 1（IGF-1）as a novel and direct target of miR-26a and revealed that miR-26a exerted its tumor-suppressor function,at least in part,by inhibiting IGF-1expression.These findings contribute to our understanding of the functions of miR-26a in osteosarcoma.
文摘MicroRNAs(miRNAs) are a class of non-coding RNAs that hybridize to mRNAs and induce either translation repression or mRNA cleavage.Recently,it has been reported that miRNAs could possibly play a critical role in cellular processes like regulation of cell growth,differentiation,and apoptosis,emphasizing their role in tumorigenesis.Likewise,several miRNA's are involved in lung cancer tumorigenesis.The present review puts forth a database of human miRNA's involved in lung cancer along with their target genes.It also provides sequences of miRNA's and their chromosomal locations retrieved from different databases like microCosm(218 microRNAs),PhenomiR(293 microRNAs),and mir2Disease(90 microRNAs) and target gene information such as the pathways like cell cycle regulation,angiogenesis,apoptosis etc.Though miRNA's are still to be explored,they hold a promise as therapeutic targets and diagnostic markers of cancer.
文摘Parkinson＇s disease（PD） is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons. Oxidative stress is also recognized as one of the main causes of PD, and excessive reactive oxygen species（ROS） and reactive nitrogen species can lead to dopaminergic neuron vulnerability and eventual death. Micro RNAs control a range of physiological and pathological functions, and may serve as potential targets for intervention against PD to mitigate damage to the brain. Several studies have demonstrated that micro RNAs can regulate oxidative stress and prevent ROS-mediated damage to dopaminergic neurons, suggesting that specific micro RNAs may be putative targets for novel therapeutic strategies in PD. Recent human and animal studies have identified a large number of dysregulated micro RNAs in PD brain tissue samples, many of which were downregulated. The dysregulated micro RNAs affect downstream targets such as SNCA, PARK2, LRRK2, TNFSF13 B, LTA, SLC5 A3, PSMB2, GSR, GBA, LAMP-2 A, HSC. Apart from one study, none of the studies reviewed had used agomirs or antagomirs to reverse the levels of downregulated or upregulated micro RNAs, respectively, in mouse models of PD or with isolated human or mouse dopaminergic cells. Further large-scale studies of brain tissue samples collected with short postmortem interval from human PD patients are warranted to provide more information on the micro RNA profiles in different brain regions and to test for gender differences.
文摘MicroRNAs (miRNAs) are a class of ~22 nucleotides long non coding RNA molecules which play an important role in gene regulation at the post transcriptional level. The conserved nature of miRNAs provides the basis of new miRNA identification through homology search. In an attempt to identify new conserved miRNAs in tea, previously known plant miRNAs were used for searching their homolog in a tea Expressed Sequence Tags and full length nucleotide sequence database. The sequences showing homolog no more than four mismatches were predicted for their fold back structures and passed through a series of filtration criteria, finally led us to identify 13 conserved miRNAs in tea belonging to 9 miRNA families. A total of 37 potential target genes in Arabidopsis were identified subsequently for 7 miRNA families based on their sequence complementarity which encode transcription factors (8%), enzymes (30%) and transporters (14%) as well as other proteins involved in physiological and metabolic processes (48%). Overall, our findings will accelerate the way for further researches of miRNAs and their functions in tea.
文摘MicroRNAs （miRNAs） are a class of newly identified, small, non-coding RNAs that play vital roles in regulation. Based on miRNAs unique features of expression pattern, evolutionary conservation, secondary structure and genetic requirements for biogenesis, computational predication strategy is adopted to predicate the novel miRNAs. In this research, potential miRNAs and their targets in grapevine （Vitis vinifera） were predicted. We used previously known plant miRNAs against grapevine genome sequence databases to search for potential miRNAs. A total of 81 potential miRNAs were detected following a range of strict filtering criteria. Using these potential miRNA sequences, we could further blast the mRNA database to find the potential targets in this species. Comparative analysis of miRNAs in grapevine and other species reveals that miRNAs exhibit an evolutional conservation, the number and function of miRNAs must have significantly expanded during the evolution of land plants. Furthermore divergence made versatile functions of miRNAs feasible. Cluster of miRNAs likely represents an ancient expression mechanism. Predicted target genes include not only transcription factors but also genes implicated in floral development, signal transduction, diseases and stress response. Till now, little is known about experimental or computational identification of miRNA in grapevine species. Increased knowledge of the biological mechanisms of the grapevine will allow targeted approaches to increase the quality of fruit and reduce the impact of parasites together with stress, which could enable a sustainable, environmentally-sound, farming policv.
文摘Traumatic brain injury （TBI） is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as develop- ment, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma （miR-425-p, -21, -93, -191 and -499） and cerebro-spinal fluid （CSF） （miR-328, -362-3p, -451, -486a） as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TBI （e.g., miR-21, miR-23b）. MicroRNA profil- ing was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TBI （e.g., miR-21） have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in microRNA profiles in different age groups （children, adults, and elderly）.
基金Supported by the National Natural Science Foundation of China(Nos.31172391,31472274)the Fundamental Research Funds for Central Universities(No.201762003)+2 种基金the Scholarship Foundation for Excellent Scientists of Shandong Province(No.BS2011SW054)the National HighTech R&D Program of China(863 Program)(No.2012AA10A402)the Open Funds of Institute of Biodiversity and Evolution,Ocean University of China(No.201362017)
文摘Study on shrimp miRNAs was limited and just 7 mature miRNA sequences of Marsupenaeus japonicus are deposited in mir Base database. In this study, miRNAs and their target gene candidates were computationally identified from shrimp Penaeu s monodon and then experimentally validated. Using 39 908 expressed sequence tags(ESTs) and 21 124 genome survey sequences(GSSs) of P. monodon(pmo) as reference dataset, a comprehensive approach based on inter-species homolog search was employed to investigate the candidate miRNAs(i.e. pmo-miRNA). A total of eight miRNAs belonging to 7 families were computationally identified and five out of them were subsequently validated by PCR and sequencing. Of these, pmo-miR-4961a, pmo-miR-4961b, pmo-miR-4979 and pmo-miR-3819 were first identified from shrimps. Both the mature pmo-miRNAs and the corresponding precursors were conserved among different species. Based on perfect or near-perfect match to the target region, the target gene candidates of pmomiRNAs were predicted from 10 331 mRNA sequences of P. monodon. A total of 20 genes were predicted as the targets of pmo-miR-4961a, pmo-miR-4961b, pmo-miR-4979 and pmo-miR-6492. Experimental validation by dual luciferase reporter assay confi rmed the targeting between 3 pmo-miRNAs and one or two of their target genes, especially the pmo-miR-4979 which could significantly down-regulate the expression of target gene(JR226772). This study updates the miRNAs and their targets in P. monodon and lays a solid foundation for future RNAi study.
文摘Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients(80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are des-perately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC.
基金supported by grants from the National Natural Science Foundation of ChinaNo.81271358+1 种基金Yunnan Science Foundation of ChinaNo.2013FZ199
文摘To determine the molecular mechanism of cerebral ischemia/reperfusion injury, we examined the micro RNA（mi RNA） expression profile in rat cortex after focal cerebral ischemia/reperfusion injury using mi RNA microarrays and bioinformatic tools to systematically analyze Gene Ontology（GO） function classifications, as well as the signaling pathways of genes targeted by these differentially expressed mi RNAs. Our results show significantly changed mi RNA expression profiles in the reperfusion period after focal cerebral ischemia, with a total of 15 mi RNAs up-regulated and 44 mi RNAs down-regulated. Target genes of these differentially expressed mi RNAs were mainly involved in metabolic and cellular processes, which were identified as hub nodes of a mi RNA-GO-network. The most correlated pathways included D-glutamine and D-glutamate metabolism, the renin-angiotensin system, peroxisomes, the PPAR signaling pathway, SNARE interactions in vesicular transport, and the calcium signaling pathway. Our study suggests that mi RNAs play an important role in the pathological process of cerebral ischemia/reperfusion injury. Understanding mi RNA expression and function may shed light on the molecular mechanism of cerebral ischemia/reperfusion injury.
文摘Primary liver cancer is a global disease that is on the increase.Hepatocellular carcinoma(HCC)accounts for most primary liver cancers and has a notably low survival rate,largely attributable to late diagnosis,resistance to treatment,tumour recurrence and metastasis.MicroRNAs(miRNAs/miRs)are regulatory RNAs that modulate protein synthesis.miRNAs are involved in several biological and pathological processes including the development and progression of HCC.Given the poor outcomes with current HCC treatments,miRNAs represent an important new target for therapeutic intervention.Several studies have demonstrated their role in HCC development and progression.While many risk factors underlie the development of HCC,one process commonly altered is iron homeostasis.Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised.Aberrant miRNA expression in hepatic fibrosis and injury response have been reported,as have dysregulated miRNA expression patterns affecting cell cycle progression,evasion of apoptosis,invasion and metastasis.In2009,miR-26a delivery was shown to prevent HCC progression,highlighting its therapeutic potential.Several studies have since investigated the clinical potential of other miRNAs with one drug,Miravirsen,currently in phaseⅡclinical trials.miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy.Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years,yielding improved HCC survival rates and patient outcomes.
基金Supported by Erwin Schroedinger Scholarship of the Austrian Science Funds,No.J3389-B23(all to Pichler M)
文摘Colorectal cancer(CRC) is the third most common cancer in western countries. Despite significant improvement in available treatment options, CRC still remains the second leading cause of cancer-related death. Traditionally, 5-fluorouracil has been used as the main chemotherapy drug for treatment of metastatic CRC(mCRC). However, during the last two decades more effective chemotherapeutic agents such as oxaliplatin, irinotecan and the monoclonal antibodies cetuximab, panitumumab and bevacizumab have been used in clinical practice. More recently, the therapeutic armamentarium has been supplemented by the monoclonal antibodies bevacizumab, cetuximab and panitumumab as well as the protein-trap aflibercept and the smallmolecule multi-kinase inhibitor regorafenib. One of the major problems for the management of CRC is the inherent or acquired resistance to therapeutic approaches. The discovery of microRNAs(miRNAs), a class of small, endogenous, non-coding, single-stranded RNAs that play a role as post-transcriptional regulators, has added new dimensions to the diagnosis and treatment of cancer. Because miRNAs are important regulators of carcinogenesis, progression, invasion, angiogenesis and metastases in CRC, they might serve as potential predictive and prognostic factors and even as therapeutic targets themselves. Several miRNAs are already known to be dysregulated in CRCs and have been linked to biological processes involved in tumor progression and response to anti-cancer therapies. This review summarizes current therapeutic approaches for treating CRC and highlights the role of miRNAs as novel predictive biomarkers and potential drug targets in CRC patients.
