Oral squamous cell carcinoma in the background of/with oral submucous fibrosis(OSCC-OSF)has a unique etiology and is clinically distinct from other OSCCs.We previously identified ADAMTS9-AS2 as a functional tumor supp...Oral squamous cell carcinoma in the background of/with oral submucous fibrosis(OSCC-OSF)has a unique etiology and is clinically distinct from other OSCCs.We previously identified ADAMTS9-AS2 as a functional tumor suppressor in OSCC-OSF through the regulation of PI3K-AKT signaling.However,its role in metabolic modulation and the underlying mechanisms remain unclear.In this study,we reported for the first time that ADAMTS9-AS2 suppressed aerobic glycolysis by cooperating with let-7a-5p in OSCC cells.Mechanistically,let-7a-5p inhibited HK2 expression by targeting its 3′-UTR,further deregulating glycolytic function,while enhancing HK2 expression rescued the inhibitory effects of the ADAMTS9-AS2/let-7a-5p axis on aerobic glycolysis and OSCC cell growth.Exosomal ADAMTS9-AS2 regulated metabolic reprogramming during OSCC tumorigenesis.ABC transporters in lipid and pyrimidine metabolism were significantly enriched pathways.Changes in several key metabolites were identified after ADAMTS9-AS2 exosome treatment,including increased levels of DL-glutamic acid and D-mannose,along with decreased levels of cytidine and D-maltose.Thus,our findings demonstrate that ADAMTS9-AS2 drives let-7a-5p binding to HK2 to suppress cell growth in OSCC by abolishing aerobic glycolysis.Our data on metabolic reprogramming have greatly expanded the role of the ADAMTS9-AS2/let-7a-5p axis as a key regulator of metabolism during OSCC tumorigenesis.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this t...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this therapy.Cancer stem cells play a crucial role in sorafenib resistance in HCC.Our previous study revealed that the long non-coding RNA(lncRNA)KIF9-AS1 is an oncogenic gene in HCC.However,the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear.Herein,we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients.Sphere formation was quantified via a tumor sphere assay.Cell viability,proliferation,and apoptosis were evaluated via Cell Counting Kit-8,flow cytometry,and colony formation assays,respectively.The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation.The tumorigenic role of KIF9-AS1 was validated in a mouse model.RESULTS Compared with that in normal controls,the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues.Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells.Mechanistically,N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1.Additionally,KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination.Furthermore,depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.展开更多
Agreen regioselective synthesis of some new and known 9-aryl-5,9-dihydropyrimido[4,5-d][l,2,4]triazolo[1,5-a]pyrimidine-6,8（4H,7H）-diones has been described via the microwave-assisted one-pot reaction of 3-amino-1H-...Agreen regioselective synthesis of some new and known 9-aryl-5,9-dihydropyrimido[4,5-d][l,2,4]triazolo[1,5-a]pyrimidine-6,8（4H,7H）-diones has been described via the microwave-assisted one-pot reaction of 3-amino-1H-1,2,4-triazoles,aromatic aldehydes and barbituric acids under solvent- and catalyst-free conditions.This operationally simple procedure is less laborious and provides a better scope than previously reported procedures.展开更多
基金supported by the National Natural Science Foundation of China(No.82460458)the Natural Science Foundation of Shanghai,China(No.21ZR1438200).
文摘Oral squamous cell carcinoma in the background of/with oral submucous fibrosis(OSCC-OSF)has a unique etiology and is clinically distinct from other OSCCs.We previously identified ADAMTS9-AS2 as a functional tumor suppressor in OSCC-OSF through the regulation of PI3K-AKT signaling.However,its role in metabolic modulation and the underlying mechanisms remain unclear.In this study,we reported for the first time that ADAMTS9-AS2 suppressed aerobic glycolysis by cooperating with let-7a-5p in OSCC cells.Mechanistically,let-7a-5p inhibited HK2 expression by targeting its 3′-UTR,further deregulating glycolytic function,while enhancing HK2 expression rescued the inhibitory effects of the ADAMTS9-AS2/let-7a-5p axis on aerobic glycolysis and OSCC cell growth.Exosomal ADAMTS9-AS2 regulated metabolic reprogramming during OSCC tumorigenesis.ABC transporters in lipid and pyrimidine metabolism were significantly enriched pathways.Changes in several key metabolites were identified after ADAMTS9-AS2 exosome treatment,including increased levels of DL-glutamic acid and D-mannose,along with decreased levels of cytidine and D-maltose.Thus,our findings demonstrate that ADAMTS9-AS2 drives let-7a-5p binding to HK2 to suppress cell growth in OSCC by abolishing aerobic glycolysis.Our data on metabolic reprogramming have greatly expanded the role of the ADAMTS9-AS2/let-7a-5p axis as a key regulator of metabolism during OSCC tumorigenesis.
基金Supported by the National Natural Science Foundation of China,No.82271628.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this therapy.Cancer stem cells play a crucial role in sorafenib resistance in HCC.Our previous study revealed that the long non-coding RNA(lncRNA)KIF9-AS1 is an oncogenic gene in HCC.However,the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear.Herein,we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients.Sphere formation was quantified via a tumor sphere assay.Cell viability,proliferation,and apoptosis were evaluated via Cell Counting Kit-8,flow cytometry,and colony formation assays,respectively.The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation.The tumorigenic role of KIF9-AS1 was validated in a mouse model.RESULTS Compared with that in normal controls,the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues.Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells.Mechanistically,N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1.Additionally,KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination.Furthermore,depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.
文摘Agreen regioselective synthesis of some new and known 9-aryl-5,9-dihydropyrimido[4,5-d][l,2,4]triazolo[1,5-a]pyrimidine-6,8（4H,7H）-diones has been described via the microwave-assisted one-pot reaction of 3-amino-1H-1,2,4-triazoles,aromatic aldehydes and barbituric acids under solvent- and catalyst-free conditions.This operationally simple procedure is less laborious and provides a better scope than previously reported procedures.
