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Topics {✒️}

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         headline:RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation
         description:Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance. AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level. Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.
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            Trastuzumab resistance
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            Cancer Research
            Oncology
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      headline:RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation
      description:Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance. AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level. Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.
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      dateModified:2022-07-11T00:00:00Z
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         Trastuzumab resistance
         Exosome
         AFAP1-AS1
         ERBB2
         Cancer Research
         Oncology
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            type:Organization
      name:Hui Cao
      affiliation:
            name:The First Affiliated Hospital of Zhengzhou University
            address:
               name:Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
               type:PostalAddress
            type:Organization
      name:Xiangke Li
      affiliation:
            name:The First Affiliated Hospital of Zhengzhou University
            address:
               name:Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
               type:PostalAddress
            type:Organization
      name:Xueke Qian
      affiliation:
            name:The First Affiliated Hospital of Zhengzhou University
            address:
               name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
               type:PostalAddress
            type:Organization
      name:Chao Yu
      affiliation:
            name:University-Town Hospital of Chongqing Medical University
            address:
               name:Department of General Surgery, University-Town Hospital of Chongqing Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
      name:Yunqing Yang
      affiliation:
            name:The First Affiliated Hospital of Zhengzhou University
            address:
               name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
               type:PostalAddress
            type:Organization
      name:Xue Yang
      affiliation:
            name:The First Affiliated Hospital of Zhengzhou University
            address:
               name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
               type:PostalAddress
            type:Organization
      name:Na Han
      affiliation:
            name:The First Affiliated Hospital of Zhengzhou University
            address:
               name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
               type:PostalAddress
            type:Organization
      name:Dongwei Dou
      affiliation:
            name:The First Affiliated Hospital of Zhengzhou University
            address:
               name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
               type:PostalAddress
            type:Organization
      name:Jianguo Hu
      affiliation:
            name:The Second Affiliated Hospital, Chongqing Medical University
            address:
               name:Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
               type:PostalAddress
            type:Organization
      name:Huaying Dong
      url:http://orcid.org/0000-0002-4905-6940
      affiliation:
            name:Hainan Affiliated Hospital of Hainan Medical University
            address:
               name:Department of General Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of General Surgery, University-Town Hospital of Chongqing Medical University, Chongqing, China
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
      name:Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
      name:Department of General Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China

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