We are analyzing https://link.springer.com/article/10.1186/s13045-019-0839-x.

Title:
M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma | Journal of Hematology & Oncology
Description:
Background Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear. Methods Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pull-down, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration. Results We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N6-methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript. A PLGA-based nanoplatform loaded with si-LINC00958 was developed for HCC systemic administration. This novel drug delivery system was controlled release, tumor targeting, safe, and presented satisfactory antitumor efficacy. Conclusions Our results delineate the clinical significance of LINC00958 in HCC and the regulatory mechanisms involved in HCC lipogenesis and progression, providing a novel prognostic indicator and promising nanotherapeutic target.
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linc, hcc, cells, nps, expression, fig, pubmed, mirp, article, hdgf, additional, cancer, google, scholar, hcclm, levels, file, tumor, overexpression, cas, level, plgapegsilinc, data, cell, assays, rna, figure, rtqpcr, hepb, group, performed, knockdown, effects, carcinoma, survival, control, shown, lipogenesis, results, analysis, chen, wang, noncoding, showed, mettl, hepatocellular, focus, tissues, sirna, pdx,

Topics {✒️}

activating beta-catenin/c-myc signaling double-emulsion solvent-diffusion technique activating wnt/beta-catenin pathway rna n6-methyladenosine methyltransferase regulating mir-3619-5p/ctnnb1 axis mir-3619-5p/hdgf signaling pathway mettl3-mediated n6-methyladenosine pmirglo-hdgf 3′-utr-mut vector biotin-labeled mir-3619-5p compared form si-linc00958/spermidine complex mir-3619-5p-silenced hep3b cells inhibiting cul4a-mediated ubiquitination linc00958/mir-3619-5p/hdgf axis article download pdf hepatoma-derived growth factor cutaneous squamous-cell carcinoma linc00202-mediated retinoblastoma progression directly targeting beta-catenin mir-3619-5p mimics led mir-3619-5p-overexpressed hcclm3 cells plga-based si-linc00958 nanoplatform rna-induced silencing complex kaplan-meier survival curves ythdf2-dependent posttranscriptional silencing broad-spectrum hdac inhibitor multi-needle electrohydrodynamic strategy anti-ago2 antibody showed plga-lipid hybrid nanoparticles linc00958/mir-3619-5p axis plga-based nanoplatform loaded mir-3619-5p hampers proliferation plga-based nanosystem ensured circ-cdyl acts specifically patient-derived xenograft model biotin-labeled mirna pull linc00958/mir-3619-5p pathway improving nanoparticle-based drug mir-3619-5p/hdgf axis beta-catenin-mediated linc00958 sponged mir-3619-5p mir-3619-5p/hdgf pathway tnm iii/iv stage tnm iii/iv group mir-3619-5p binding site transfecting mir-3619-5p mimics mir-3619-5p inhibitor presented long noncoding rnas kaplan-meier curves sponge mir-590-3p/mir-1275 linc00958-mediated hcc progression

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         headline:M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma
         description:Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear. Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pull-down, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration. We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N6-methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript. A PLGA-based nanoplatform loaded with si-LINC00958 was developed for HCC systemic administration. This novel drug delivery system was controlled release, tumor targeting, safe, and presented satisfactory antitumor efficacy. Our results delineate the clinical significance of LINC00958 in HCC and the regulatory mechanisms involved in HCC lipogenesis and progression, providing a novel prognostic indicator and promising nanotherapeutic target.
         datePublished:2020-01-08T00:00:00Z
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            Hepatocellular carcinoma
            N6-methyladenosine
            Lipogenesis
            HDGF
            Oncology
            Hematology
            Cancer Research
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      headline:M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma
      description:Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear. Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pull-down, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration. We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N6-methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript. A PLGA-based nanoplatform loaded with si-LINC00958 was developed for HCC systemic administration. This novel drug delivery system was controlled release, tumor targeting, safe, and presented satisfactory antitumor efficacy. Our results delineate the clinical significance of LINC00958 in HCC and the regulatory mechanisms involved in HCC lipogenesis and progression, providing a novel prognostic indicator and promising nanotherapeutic target.
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      dateModified:2020-01-08T00:00:00Z
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         LINC00958
         Hepatocellular carcinoma
         N6-methyladenosine
         Lipogenesis
         HDGF
         Oncology
         Hematology
         Cancer Research
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      affiliation:
            name:The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College
            address:
               name:Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, China
               type:PostalAddress
            type:Organization
            name:The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation
            address:
               name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
               type:PostalAddress
            type:Organization
            name:Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College)
            address:
               name:Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, China
               type:PostalAddress
            type:Organization
      name:Zhiqiang Chen
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation
            address:
               name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Wen Gao
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University
            address:
               name:Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Yao Zhang
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation
            address:
               name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Jinguo Wang
      affiliation:
            name:The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College
            address:
               name:Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, China
               type:PostalAddress
            type:Organization
      name:Junfeng Wang
      affiliation:
            name:The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College
            address:
               name:Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, China
               type:PostalAddress
            type:Organization
      name:Ming Cao
      affiliation:
            name:Anhui University
            address:
               name:Key Laboratory of Environment-Friendly Polymeric Materials of Anhui Province, School of Chemistry and Chemical Engineering, Anhui University, Hefei, China
               type:PostalAddress
            type:Organization
      name:Juan Cai
      affiliation:
            name:Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College)
            address:
               name:Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, China
               type:PostalAddress
            type:Organization
            name:The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College
            address:
               name:Department of Oncology, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, China
               type:PostalAddress
            type:Organization
            name:Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University
            address:
               name:The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Jindao Wu
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation
            address:
               name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
               type:PostalAddress
            type:Organization
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Xuehao Wang
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation
            address:
               name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, China
      name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
      name:Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, China
      name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
      name:Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
      name:Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, China
      name:Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, China
      name:Key Laboratory of Environment-Friendly Polymeric Materials of Anhui Province, School of Chemistry and Chemical Engineering, Anhui University, Hefei, China
      name:Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, China
      name:Department of Oncology, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, China
      name:The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
      name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
      name:Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation, Nanjing, China

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