BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancre...BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.展开更多
BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 p...BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.展开更多
N6-methyladenosine(m6A)is a reversible epigenetic modification, which is one of the most abundant modifiers in eukaryotic cells and has been commonly reported in messenger RNAs and non-coding RNAs. The processing modi...N6-methyladenosine(m6A)is a reversible epigenetic modification, which is one of the most abundant modifiers in eukaryotic cells and has been commonly reported in messenger RNAs and non-coding RNAs. The processing modification of m6A regulates RNA transcription, processing, splicing, degradation, and translation, and plays an important role in the biological process of tumors. Circular RNA, which lacks the 5' cap structure, has been mistakenly regarded as a "junk sequence" generated by accidental shearing during the transcription process. However, it has been found that circRNAs can be involved in tumor invasion and metastasis through microRNAs, binding proteins, translated peptides, and m6A modifications. In this paper, we reviewed the role of m6A modifications in circRNA regulation and their functions in hepatocellular carcinoma and discussed their potential clinical applications and future development in this field.展开更多
Within the context of the Belt and Road Initiative(BRI)and the China-Myanmar Economic Corridor(CMEC),the Dulong-Ir-rawaddy(Ayeyarwady)River,an international river among China,India and Myanmar,plays a significant role...Within the context of the Belt and Road Initiative(BRI)and the China-Myanmar Economic Corridor(CMEC),the Dulong-Ir-rawaddy(Ayeyarwady)River,an international river among China,India and Myanmar,plays a significant role as both a valuable hydro-power resource and an essential ecological passageway.However,the water resources and security exhibit a high degree of vulnerabil-ity to climate change impacts.This research evaluates climate impacts on the hydrology of the Dulong-Irrawaddy River Basin(DIRB)by using a physical-based hydrologic model.We crafted future climate scenarios using the three latest global climate models(GCMs)from Coupled Model Intercomparison Project 6(CMIP6)under two shared socioeconomic pathways(SSP2-4.5 and SSP5-8.5)for the near(2025-2049),mid(2050-2074),and far future(2075-2099).The regional model using MIKE SHE based on historical hydrologic processes was developed to further project future streamflow,demonstrating reliable performance in streamflow simulations with a val-idation Nash-Sutcliffe Efficiency(NSE)of 0.72.Results showed that climate change projections showed increases in the annual precip-itation and potential evapotranspiration(PET),with precipitation increasing by 11.3%and 26.1%,and PET increasing by 3.2%and 4.9%,respectively,by the end of the century under SSP2-4.5 and SSP5-8.5.These changes are projected to result in increased annual streamflow at all stations,notably at the basin’s outlet(Pyay station)compared to the baseline period(with an increase of 16.1%and 37.0%at the end of the 21st century under SSP2-4.5 and SSP5-8.5,respectively).Seasonal analysis for Pyay station forecasts an in-crease in dry-season streamflow by 31.3%-48.9%and 22.5%-76.3%under SSP2-4.5 and SSP5-8.5,respectively,and an increase in wet-season streamflow by 5.8%-12.6%and 2.8%-33.3%,respectively.Moreover,the magnitude and frequency of flood events are pre-dicted to escalate,potentially impacting hydropower production and food security significantly.This research outlines the hydrological response to future climate change during the 21st century and offers a scientific basis for the water resource management strategies by decision-makers.展开更多
基金Supported by National Natural Science Foundation of China,No.81802450and Natural Science Foundation of Hunan Province,No.2020JJ4133 and No.2021JJ31135.
文摘BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.
基金Natural Science Foundation of Shandong Province,No.ZR2020MH207 and No.ZR2020MH251.
文摘BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.
基金Key Project Research and Development Plan of Hainan Province(No.ZDYF2020134,ZDYF2022SHFZ283)Natural Science Foundation of Hainan Province(No.821QN391)。
文摘N6-methyladenosine(m6A)is a reversible epigenetic modification, which is one of the most abundant modifiers in eukaryotic cells and has been commonly reported in messenger RNAs and non-coding RNAs. The processing modification of m6A regulates RNA transcription, processing, splicing, degradation, and translation, and plays an important role in the biological process of tumors. Circular RNA, which lacks the 5' cap structure, has been mistakenly regarded as a "junk sequence" generated by accidental shearing during the transcription process. However, it has been found that circRNAs can be involved in tumor invasion and metastasis through microRNAs, binding proteins, translated peptides, and m6A modifications. In this paper, we reviewed the role of m6A modifications in circRNA regulation and their functions in hepatocellular carcinoma and discussed their potential clinical applications and future development in this field.
基金Under the auspices of the Yunnan Scientist Workstation on International River Research of Daming He(No.KXJGZS-2019-005)National Natural Science Foundation of China(No.42201040)+1 种基金National Key Research and Development Project of China(No.2016YFA0601601)China Postdoctoral Science Foundation(No.2023M733006)。
文摘Within the context of the Belt and Road Initiative(BRI)and the China-Myanmar Economic Corridor(CMEC),the Dulong-Ir-rawaddy(Ayeyarwady)River,an international river among China,India and Myanmar,plays a significant role as both a valuable hydro-power resource and an essential ecological passageway.However,the water resources and security exhibit a high degree of vulnerabil-ity to climate change impacts.This research evaluates climate impacts on the hydrology of the Dulong-Irrawaddy River Basin(DIRB)by using a physical-based hydrologic model.We crafted future climate scenarios using the three latest global climate models(GCMs)from Coupled Model Intercomparison Project 6(CMIP6)under two shared socioeconomic pathways(SSP2-4.5 and SSP5-8.5)for the near(2025-2049),mid(2050-2074),and far future(2075-2099).The regional model using MIKE SHE based on historical hydrologic processes was developed to further project future streamflow,demonstrating reliable performance in streamflow simulations with a val-idation Nash-Sutcliffe Efficiency(NSE)of 0.72.Results showed that climate change projections showed increases in the annual precip-itation and potential evapotranspiration(PET),with precipitation increasing by 11.3%and 26.1%,and PET increasing by 3.2%and 4.9%,respectively,by the end of the century under SSP2-4.5 and SSP5-8.5.These changes are projected to result in increased annual streamflow at all stations,notably at the basin’s outlet(Pyay station)compared to the baseline period(with an increase of 16.1%and 37.0%at the end of the 21st century under SSP2-4.5 and SSP5-8.5,respectively).Seasonal analysis for Pyay station forecasts an in-crease in dry-season streamflow by 31.3%-48.9%and 22.5%-76.3%under SSP2-4.5 and SSP5-8.5,respectively,and an increase in wet-season streamflow by 5.8%-12.6%and 2.8%-33.3%,respectively.Moreover,the magnitude and frequency of flood events are pre-dicted to escalate,potentially impacting hydropower production and food security significantly.This research outlines the hydrological response to future climate change during the 21st century and offers a scientific basis for the water resource management strategies by decision-makers.
