Piwi-interacting Ribonucleic acids(piRNAs)molecule is a wellknown subclass of small non-codingRNAmolecules that are mainly responsible for maintaining genome integrity,regulating gene expression,and germline stem cell...Piwi-interacting Ribonucleic acids(piRNAs)molecule is a wellknown subclass of small non-codingRNAmolecules that are mainly responsible for maintaining genome integrity,regulating gene expression,and germline stem cell maintenance by suppressing transposon elements.The piRNAs molecule can be used for the diagnosis of multiple tumor types and drug development.Due to the vital roles of the piRNA in computational biology,the identification of piRNAs has become an important area of research in computational biology.This paper proposes a two-layer predictor to improve the prediction of piRNAs and their function using deep learning methods.The proposed model applies various feature extraction methods to consider both structure information and physicochemical properties of the biological sequences during the feature extraction process.The outcome of the proposed model is extensively evaluated using the k-fold cross-validation method.The evaluation result shows that the proposed predictor performed better than the existing models with accuracy improvement of 7.59%and 2.81%at layer I and layer II respectively.It is anticipated that the proposed model could be a beneficial tool for cancer diagnosis and precision medicine.展开更多
PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as ti...PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and stemness.Additionally,the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors.Nonetheless,the precise functions of pi RNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended.This review aims to examine current research on the biogenesis and functions of pi RNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of pi RNAs and piwi proteins in the management and treatment of advanced cancer.展开更多
PIWI-interacting RNA(piRNAs),once thought to be mainly functioning in germlines,are now known to play an essential role in somatic and cancerous tissues.Ping-pong cycle initi-ation and mitochondria-based phased produc...PIWI-interacting RNA(piRNAs),once thought to be mainly functioning in germlines,are now known to play an essential role in somatic and cancerous tissues.Ping-pong cycle initi-ation and mitochondria-based phased production constitute the core of the piRNA biogenesis and these two processes are well conserved in mammals,including humans.By being involved in DNA methylation,histone marker deposition,mRNA degradation,and protein modification,piRNAs also contribute to carcinogenesis partly due to oncogenic stress-induced piRNA dysre-gulation.Also,piRNAs play important roles in cancer stemness,drug resistance,and tumor immunology.Results from liquid biopsy analysis of piRNA can be used in both cancer diagnoses and cancer prognoses.A combination of targeting piRNA with other therapeutic strategies could be groundbreaking cancer treatment.展开更多
Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global health.Understanding the molecular mechanisms underlying the development...Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global health.Understanding the molecular mechanisms underlying the development and progression of HCC is central to improving our clinical approaches.PIWIinteracting RNAs(piRNAs)are a class of small non-coding RNAs that bind to PIWI family proteins to regulate gene expression at transcriptional and posttranscriptional levels.A growing body of work shows that the dysregulation of piRNAs plays a crucial role in the progression of various human cancers.In this editorial,we report on the current knowledge of HCC-associated piRNAs and their potential clinical utility.Based on the editorial by Papadopoulos and Trifylli,on the role and clinical evaluation of exosomal circular RNAs in HCC,we highlight this other emerging class of non-coding RNAs.展开更多
Noncoding RNAs(nc RNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of nc RNAs has been reported i...Noncoding RNAs(nc RNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of nc RNAs has been reported in tumor initiation, progression, invasion and metastasis in various cancers, including gastric cancer(GC). In the past few years, an accumulating body of evidence has deepened our understanding of nc RNAs, and several emerging nc RNAs have been identified, such as PIWI-interacting RNAs(pi RNAs) and circular RNAs(circ RNAs). The competing endogenous RNA(ce RNA) networks include m RNAs, micro RNAs, long nc RNAs(lnc RNAs) and circ RNAs, which play critical roles in the tumorigenesis of GC. This review summarizes the recent hotspots of nc RNAs involved in GC pathobiology and their potential applications in GC. Finally, we briefly discuss the advances in the ce RNA network in GC.展开更多
Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expressi...Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.展开更多
The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various stressors.The foremost among these is the threat posed by oxidative stress,...The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various stressors.The foremost among these is the threat posed by oxidative stress,which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids,proteins,and nucleic acids.In mice,the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5(GPX5)as a major luminal scavenger in the proximal caput epididymidal segment.Accordingly,the loss of GPX5^-/-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx57 mice.To explore the underlying mechanism,we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged(13 months old)Gpx5^-/-m mice.This analysis revealed the dysregulation of several thousand epididymal mRNA transcripts,in eluding the downregulation of a subgroup of piRNA pathway gen es,in aged Gpx5^-/-mice.In agreeme nt with these fin dings,we also observed the loss of piRNAs,which potentially bind to the P-element-induced wimpy testis(PlWI)-like proteins PIWIL1 and PIWIL2.The absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5^-/-mice.Importantly,the oxidative stress response genes tend to have more targeting piRNAs,and many of them were among the top increased genes upon the loss of GPX5^-/-.Taken together,our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible invoIvement in the aging and oxidative stress-mediated responses.展开更多
Inhibiting retinal neovascularization is the optimal strategy for the treatment of retina-related diseases, but there is currently no effective treatment for retinal neovascularization. P-element-induced wimpy testis(...Inhibiting retinal neovascularization is the optimal strategy for the treatment of retina-related diseases, but there is currently no effective treatment for retinal neovascularization. P-element-induced wimpy testis(PIWI)-interacting RNA(piRNA) is a type of small non-coding RNA implicated in a variety of diseases. In this study, we found that the expression of piR-1245 and the interacting protein PIWIL2 were remarkably increased in human retinal endothelial cells cultured in a hypoxic environment, and cell apoptosis, migration, tube formation and proliferation were remarkably enhanced in these cells. Knocking down piR-1245 inhibited the above phenomena. After intervention by a p-JAK2 activator, piR-1245 decreased the expression of hypoxia inducible factor-1α and vascular endothelial growth factor through the JAK2/STAT3 pathway. For in vivo analysis, 7-day-old newborn mice were raised in 75 ± 2% hyperoxia for 5 days and then piR-1245 in the retina was knocked down. In these mice, the number of newly formed vessels in the retina was decreased, the expressions of inflammationrelated proteins were reduced, the number of apoptotic cells in the retina was decreased, the JAK2/STAT3 pathway was inhibited, and the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor were decreased. Injection of the JAK2 inhibitor JAK2/TYK2-IN-1 into the vitreous cavity inhibited retinal neovascularization in mice and reduced expression of hypoxia inducible factor-1α and vascular endothelial growth factor. These findings suggest that piR-1245 activates the JAK2/STAT3 pathway, regulates the expression of hypoxia inducible factor-1α and vascular endothelial growth factor, and promotes retinal neovascularization. Therefore, piR-1245 may be a new therapeutic target for retinal neovascularization.展开更多
Human rhinovirus(HRV)is one of the most important cold-causing pathogens in humans.Piwi-interacting RNAs(piRNAs)are a recently discovered class of small non-coding RNAs whose best-understood function is to repress mob...Human rhinovirus(HRV)is one of the most important cold-causing pathogens in humans.Piwi-interacting RNAs(piRNAs)are a recently discovered class of small non-coding RNAs whose best-understood function is to repress mobile element(ME)activity in animal germline.However,the profile of human/host piRNA during HRV infection is largely unknown.Here we performed high-throughput sequencing of piRNAs from H1-HeLa cells infected with HRV16 at 12 h,24 h,and 36 h.The results showed that 22,151,664,24,362,486 and 22,726,546 piRNAs displayed differential expression after HRV16 infection for three time points.A significant differential expression of 21 piRNAs was found in all time points and further verified by RT-qPCR,including 7 known piRNAs and 14 newly found piRNAs.In addition,piRNA prediction was performed on Piano using the SVM algorithm and transposon information.It found that novel_pir78110,novel_pir78107,novel_pir78097,novel_pir78094 and novel_pir76584 are associated with the DNA/hobo of Drosophila,Ac of maize and Tam3 of snapdragon(hAT)-Charlie transposon.The novel_pir97924,novel_pir105705 and novel_pir105700 recognize long interspersed nuclear elements 1(LINE-1).The novel_pir33182 and novel_pir46604 are related to the long terminal repeat(LTR)/(Endogenous Retrovirus1)ERV1 repetitive element.The novel_pir73855 is related to the LTR/ERVK repetitive element.Both novel_pir70108 and novel_pir70106 are associated with the LTR/ERVL-MaLR repetitive element.The novel_pir15900 is associated with the DNA/hAT-Tip100 repetitive element.Overall,our results indicated that rhinovirus infection could reduce the expression of some piRNAs to facilitate upregulation of LINE-1 transcription or retrotransposons'expression,which is helpful to further explore the mechanism of rhinovirus infection.展开更多
Currently,extracellular vesicles and particularly exosomes have gained a lot of research interest due to their unique roles in several biological processes.Noncoding RNAs(microRNAs,long noncoding RNAs and circular RNA...Currently,extracellular vesicles and particularly exosomes have gained a lot of research interest due to their unique roles in several biological processes.Noncoding RNAs(microRNAs,long noncoding RNAs and circular RNAs)represent a class of functional RNA with distinct regulatory roles in tumorigenesis and cancer progression.Cholangiocarcinoma is a rare but highly aggressive type of malignancy that is very challenging to diagnose,especially in early stages;surgical resection still represents the sole potentially curative treatment option.Hence,there is an urgent need for the discovery of novel diagnostic and prognostic biomarkers.Hereby,we provide a comprehensive review of the most recent discoveries that focus on exosomal noncoding RNAs in cholangiocarcinoma with the aim to identify new molecular players that could be used as biomarkers and therapeutic targets.展开更多
The Piwi-interacting RNA(piRNA)pathway has been shown to be involved in the antiviral defense against RNA viruses,especially in mosquitoes,but its universality has been questioned.Here,we used the Bombyx mori nucleopo...The Piwi-interacting RNA(piRNA)pathway has been shown to be involved in the antiviral defense against RNA viruses,especially in mosquitoes,but its universality has been questioned.Here,we used the Bombyx mori nucleopolyhedrovirus(BmNPV)-infected silkworm as a model to explore the effects of the key factors of piRNA pathway,BmAgo3 and Siwi,on replication of a large DNA virus(belonging to the family of Baculoviridae).We demonstrated that BmAgo3 and Siwi could promote the replication of BmNPV through both overexpression and knockdown experiments in BmN cell lines and silkworm larvae.In addition,we also studied the effect of PIWI-class genes on Autographa californica nucleopolyhedrovirus(AcMNPV)replication in the Spodoptera frugiperda cell line Sf9.By knocking down the expression of PIWI-class genes in Sf9,we found that Piwi-like-1 and Piwi-like-2-3 could inhibit AcMNPV replication,while Piwi-like-4-5 promoted virus replication.Our study provides compelling evidence that the piRNA pathway affects host infection by exogenous viruses in Lepidoptera.Also,our results reflect the diversity of the roles of PIWI-class genes in virus infection of the host across species.This study is the first to explore the interaction of PIWI-class proteins with DNA viruses,providing new insights into the functional roles of the piRNA pathway.展开更多
Diabrotica virgifera virgifera(western corn rootworm,WCR)is one of the most destructive agricultural insect pests in North America.It is highly adaptive to environmental stimuli and crop protection technologies.Howeve...Diabrotica virgifera virgifera(western corn rootworm,WCR)is one of the most destructive agricultural insect pests in North America.It is highly adaptive to environmental stimuli and crop protection technologies.However,little is known about the underlying genetic basis of WCR behavior and adaptation.More specifically,the involvement of small RNAs(s RNAs),especially micro RNAs(mi RNAs),a class of endogenous small non-coding RNAs that regulate various biological processes,has not been examined,and the datasets of putative s RNA sequences have not previously been generated for WCR.To achieve a comprehensive collection of s RNA transcriptomes in WCR,we constructed,sequenced,and analyzed s RNA libraries from different life stages of WCR and northern corn rootworm(NCR),and identified 101 conserved precursor mi RNAs(pre-mi RNAs)in WCR and other Arthropoda.We also identified 277 corn rootworm specific pre-mi RNAs.Systematic analyses of s RNA populations in WCR revealed that its s RNA transcriptome,which includes PIWI-interacting RNAs(pi RNAs)and mi RNAs,undergoes a dynamic change throughout insect development.Phylogenetic analysis of mi RNA datasets from model species reveals that a large pool of species-specific mi RNAs exists in corn rootworm;these are potentially evolutionarily transient.Comparisons of WCR mi RNA clusters to other insect species highlight conserved mi RNA-regulated processes that are common to insects.Parallel Analysis of RNA Ends(PARE)also uncovered potential mi RNA-guided cleavage sites in WCR.Overall,this study provides a new resource for studying the s RNA transcriptome and mi RNA-mediated gene regulation in WCR and other Coleopteran insects.展开更多
基金This research was supported by the Ministry of Higher Education(MOHE)of Malaysia through Fundamental Research Grant Scheme(FRGS/1/2020/ICT02/UPM/02/3).
文摘Piwi-interacting Ribonucleic acids(piRNAs)molecule is a wellknown subclass of small non-codingRNAmolecules that are mainly responsible for maintaining genome integrity,regulating gene expression,and germline stem cell maintenance by suppressing transposon elements.The piRNAs molecule can be used for the diagnosis of multiple tumor types and drug development.Due to the vital roles of the piRNA in computational biology,the identification of piRNAs has become an important area of research in computational biology.This paper proposes a two-layer predictor to improve the prediction of piRNAs and their function using deep learning methods.The proposed model applies various feature extraction methods to consider both structure information and physicochemical properties of the biological sequences during the feature extraction process.The outcome of the proposed model is extensively evaluated using the k-fold cross-validation method.The evaluation result shows that the proposed predictor performed better than the existing models with accuracy improvement of 7.59%and 2.81%at layer I and layer II respectively.It is anticipated that the proposed model could be a beneficial tool for cancer diagnosis and precision medicine.
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province(2022A1515220184)the Natural Science Foundation of Guangdong Province(2021A1515010547)。
文摘PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and stemness.Additionally,the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors.Nonetheless,the precise functions of pi RNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended.This review aims to examine current research on the biogenesis and functions of pi RNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of pi RNAs and piwi proteins in the management and treatment of advanced cancer.
文摘PIWI-interacting RNA(piRNAs),once thought to be mainly functioning in germlines,are now known to play an essential role in somatic and cancerous tissues.Ping-pong cycle initi-ation and mitochondria-based phased production constitute the core of the piRNA biogenesis and these two processes are well conserved in mammals,including humans.By being involved in DNA methylation,histone marker deposition,mRNA degradation,and protein modification,piRNAs also contribute to carcinogenesis partly due to oncogenic stress-induced piRNA dysre-gulation.Also,piRNAs play important roles in cancer stemness,drug resistance,and tumor immunology.Results from liquid biopsy analysis of piRNA can be used in both cancer diagnoses and cancer prognoses.A combination of targeting piRNA with other therapeutic strategies could be groundbreaking cancer treatment.
文摘Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global health.Understanding the molecular mechanisms underlying the development and progression of HCC is central to improving our clinical approaches.PIWIinteracting RNAs(piRNAs)are a class of small non-coding RNAs that bind to PIWI family proteins to regulate gene expression at transcriptional and posttranscriptional levels.A growing body of work shows that the dysregulation of piRNAs plays a crucial role in the progression of various human cancers.In this editorial,we report on the current knowledge of HCC-associated piRNAs and their potential clinical utility.Based on the editorial by Papadopoulos and Trifylli,on the role and clinical evaluation of exosomal circular RNAs in HCC,we highlight this other emerging class of non-coding RNAs.
基金Supported by National Natural Science Foundation of China,No.81472220Shanghai Science and Technology Development Fund,Domestic Science and Technology Cooperation Project,No.14495800300
文摘Noncoding RNAs(nc RNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of nc RNAs has been reported in tumor initiation, progression, invasion and metastasis in various cancers, including gastric cancer(GC). In the past few years, an accumulating body of evidence has deepened our understanding of nc RNAs, and several emerging nc RNAs have been identified, such as PIWI-interacting RNAs(pi RNAs) and circular RNAs(circ RNAs). The competing endogenous RNA(ce RNA) networks include m RNAs, micro RNAs, long nc RNAs(lnc RNAs) and circ RNAs, which play critical roles in the tumorigenesis of GC. This review summarizes the recent hotspots of nc RNAs involved in GC pathobiology and their potential applications in GC. Finally, we briefly discuss the advances in the ce RNA network in GC.
基金Supported by National Natural Science Foundation of China,No.81171660Zhejiang Provincial Natural Science Foundation of China,No.Y14C060003+4 种基金Natural Science Foundation of Ningbo,No.2012A610207The Scientific Innovation Team Project of Ningbo,No.2011B82014The Project of Key Disciplines in Ningbo,No.XKL11D2127 and No.XKL11D2128Foundation of Zhejiang Provincial Key Laboratory of Pathophysiology,No.201301K.C.Wong Magna Fund in Ningbo University
文摘Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.
基金This research was supported by the National Basic Research Program of China(Grant No.2014CB943103)National Natural Science Foundation of China(Grant No.31471104,No.31671203,No.31301225,No.31301226,No.31701119,and No.31571192)and was partly realized under the frame of the France-China scientific exchange programs"Xu Guangqi"and"Cai Yuanpei"of the"Partenariat Hubert CurienM attributed to J RD and YLZ The authors thank Prof.Winnie Wai Chi Shum,Prof.Xiaodong Sun,Ms.Aihua Liu,Dr.Chaobao Zhang,Dr.Zhen Lin,Dr.Xueting Luo,and the Bio-Med Big Data Center,CAS-MPG Partner Institute for Computational Biology,Shanghai Institutes for Biological Sciences,and Chinese Academy of Sciences for their kind support.
文摘The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various stressors.The foremost among these is the threat posed by oxidative stress,which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids,proteins,and nucleic acids.In mice,the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5(GPX5)as a major luminal scavenger in the proximal caput epididymidal segment.Accordingly,the loss of GPX5^-/-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx57 mice.To explore the underlying mechanism,we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged(13 months old)Gpx5^-/-m mice.This analysis revealed the dysregulation of several thousand epididymal mRNA transcripts,in eluding the downregulation of a subgroup of piRNA pathway gen es,in aged Gpx5^-/-mice.In agreeme nt with these fin dings,we also observed the loss of piRNAs,which potentially bind to the P-element-induced wimpy testis(PlWI)-like proteins PIWIL1 and PIWIL2.The absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5^-/-mice.Importantly,the oxidative stress response genes tend to have more targeting piRNAs,and many of them were among the top increased genes upon the loss of GPX5^-/-.Taken together,our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible invoIvement in the aging and oxidative stress-mediated responses.
基金supported by the National Natural Science Foundation of China,No. 81570866 (to XLC)。
文摘Inhibiting retinal neovascularization is the optimal strategy for the treatment of retina-related diseases, but there is currently no effective treatment for retinal neovascularization. P-element-induced wimpy testis(PIWI)-interacting RNA(piRNA) is a type of small non-coding RNA implicated in a variety of diseases. In this study, we found that the expression of piR-1245 and the interacting protein PIWIL2 were remarkably increased in human retinal endothelial cells cultured in a hypoxic environment, and cell apoptosis, migration, tube formation and proliferation were remarkably enhanced in these cells. Knocking down piR-1245 inhibited the above phenomena. After intervention by a p-JAK2 activator, piR-1245 decreased the expression of hypoxia inducible factor-1α and vascular endothelial growth factor through the JAK2/STAT3 pathway. For in vivo analysis, 7-day-old newborn mice were raised in 75 ± 2% hyperoxia for 5 days and then piR-1245 in the retina was knocked down. In these mice, the number of newly formed vessels in the retina was decreased, the expressions of inflammationrelated proteins were reduced, the number of apoptotic cells in the retina was decreased, the JAK2/STAT3 pathway was inhibited, and the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor were decreased. Injection of the JAK2 inhibitor JAK2/TYK2-IN-1 into the vitreous cavity inhibited retinal neovascularization in mice and reduced expression of hypoxia inducible factor-1α and vascular endothelial growth factor. These findings suggest that piR-1245 activates the JAK2/STAT3 pathway, regulates the expression of hypoxia inducible factor-1α and vascular endothelial growth factor, and promotes retinal neovascularization. Therefore, piR-1245 may be a new therapeutic target for retinal neovascularization.
基金This work was supported by the China MegaProject for Infectious Disease(2018ZX10102001,2018ZX10711001,2018ZX10734401 and 2018ZX10734404)the SKLID Development Grant(2011SKLID104).
文摘Human rhinovirus(HRV)is one of the most important cold-causing pathogens in humans.Piwi-interacting RNAs(piRNAs)are a recently discovered class of small non-coding RNAs whose best-understood function is to repress mobile element(ME)activity in animal germline.However,the profile of human/host piRNA during HRV infection is largely unknown.Here we performed high-throughput sequencing of piRNAs from H1-HeLa cells infected with HRV16 at 12 h,24 h,and 36 h.The results showed that 22,151,664,24,362,486 and 22,726,546 piRNAs displayed differential expression after HRV16 infection for three time points.A significant differential expression of 21 piRNAs was found in all time points and further verified by RT-qPCR,including 7 known piRNAs and 14 newly found piRNAs.In addition,piRNA prediction was performed on Piano using the SVM algorithm and transposon information.It found that novel_pir78110,novel_pir78107,novel_pir78097,novel_pir78094 and novel_pir76584 are associated with the DNA/hobo of Drosophila,Ac of maize and Tam3 of snapdragon(hAT)-Charlie transposon.The novel_pir97924,novel_pir105705 and novel_pir105700 recognize long interspersed nuclear elements 1(LINE-1).The novel_pir33182 and novel_pir46604 are related to the long terminal repeat(LTR)/(Endogenous Retrovirus1)ERV1 repetitive element.The novel_pir73855 is related to the LTR/ERVK repetitive element.Both novel_pir70108 and novel_pir70106 are associated with the LTR/ERVL-MaLR repetitive element.The novel_pir15900 is associated with the DNA/hAT-Tip100 repetitive element.Overall,our results indicated that rhinovirus infection could reduce the expression of some piRNAs to facilitate upregulation of LINE-1 transcription or retrotransposons'expression,which is helpful to further explore the mechanism of rhinovirus infection.
文摘Currently,extracellular vesicles and particularly exosomes have gained a lot of research interest due to their unique roles in several biological processes.Noncoding RNAs(microRNAs,long noncoding RNAs and circular RNAs)represent a class of functional RNA with distinct regulatory roles in tumorigenesis and cancer progression.Cholangiocarcinoma is a rare but highly aggressive type of malignancy that is very challenging to diagnose,especially in early stages;surgical resection still represents the sole potentially curative treatment option.Hence,there is an urgent need for the discovery of novel diagnostic and prognostic biomarkers.Hereby,we provide a comprehensive review of the most recent discoveries that focus on exosomal noncoding RNAs in cholangiocarcinoma with the aim to identify new molecular players that could be used as biomarkers and therapeutic targets.
基金supported by Guangzhou Science and Technology Plan(202201010369)Natural Science Foundation of Guangdong Basic and Applied Basic Research Fund(2022A1515012657)+2 种基金National Natural Science Foundation of China(31872426)South China Agricultural University high-level talent launch projectand Guangdong Provincial Promotion Project on Preservation and Utilization of Local Breed of Livestock and Poultry(No.2018-143).
文摘The Piwi-interacting RNA(piRNA)pathway has been shown to be involved in the antiviral defense against RNA viruses,especially in mosquitoes,but its universality has been questioned.Here,we used the Bombyx mori nucleopolyhedrovirus(BmNPV)-infected silkworm as a model to explore the effects of the key factors of piRNA pathway,BmAgo3 and Siwi,on replication of a large DNA virus(belonging to the family of Baculoviridae).We demonstrated that BmAgo3 and Siwi could promote the replication of BmNPV through both overexpression and knockdown experiments in BmN cell lines and silkworm larvae.In addition,we also studied the effect of PIWI-class genes on Autographa californica nucleopolyhedrovirus(AcMNPV)replication in the Spodoptera frugiperda cell line Sf9.By knocking down the expression of PIWI-class genes in Sf9,we found that Piwi-like-1 and Piwi-like-2-3 could inhibit AcMNPV replication,while Piwi-like-4-5 promoted virus replication.Our study provides compelling evidence that the piRNA pathway affects host infection by exogenous viruses in Lepidoptera.Also,our results reflect the diversity of the roles of PIWI-class genes in virus infection of the host across species.This study is the first to explore the interaction of PIWI-class proteins with DNA viruses,providing new insights into the functional roles of the piRNA pathway.
基金supported by the Dow Agro SciencesFunding from Beijing Academy of Agriculture and Forestry Sciences(Grant Nos.KJCX20180425 and KJCX20180204 to XY)。
文摘Diabrotica virgifera virgifera(western corn rootworm,WCR)is one of the most destructive agricultural insect pests in North America.It is highly adaptive to environmental stimuli and crop protection technologies.However,little is known about the underlying genetic basis of WCR behavior and adaptation.More specifically,the involvement of small RNAs(s RNAs),especially micro RNAs(mi RNAs),a class of endogenous small non-coding RNAs that regulate various biological processes,has not been examined,and the datasets of putative s RNA sequences have not previously been generated for WCR.To achieve a comprehensive collection of s RNA transcriptomes in WCR,we constructed,sequenced,and analyzed s RNA libraries from different life stages of WCR and northern corn rootworm(NCR),and identified 101 conserved precursor mi RNAs(pre-mi RNAs)in WCR and other Arthropoda.We also identified 277 corn rootworm specific pre-mi RNAs.Systematic analyses of s RNA populations in WCR revealed that its s RNA transcriptome,which includes PIWI-interacting RNAs(pi RNAs)and mi RNAs,undergoes a dynamic change throughout insect development.Phylogenetic analysis of mi RNA datasets from model species reveals that a large pool of species-specific mi RNAs exists in corn rootworm;these are potentially evolutionarily transient.Comparisons of WCR mi RNA clusters to other insect species highlight conserved mi RNA-regulated processes that are common to insects.Parallel Analysis of RNA Ends(PARE)also uncovered potential mi RNA-guided cleavage sites in WCR.Overall,this study provides a new resource for studying the s RNA transcriptome and mi RNA-mediated gene regulation in WCR and other Coleopteran insects.
