Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6
Long noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung canc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-02-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897231154574 |
| _version_ | 1811163067631796224 |
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| author | Jiantao Wang Chuan Yang Huan Cao Jianwang Yang Wenxia Meng Miaomiao Yu Lei Yu Baoshan Wang |
| author_facet | Jiantao Wang Chuan Yang Huan Cao Jianwang Yang Wenxia Meng Miaomiao Yu Lei Yu Baoshan Wang |
| author_sort | Jiantao Wang |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung cancer. However, the functions of MAGI2-AS3 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, MAGI2-AS3 expression level in LSCC tissue and cell lines was detected, and the effect of MAGI2-AS3 overexpressed on LSCC phenotypes and the possible influence mechanisms were examined. MAGI2-AS3 was downregulated in the tissues of LSCC patients versus non-tumor tissues, and it was correlated with advanced TNM (tumor, node, metastasis) stage and lymph node metastases, as indicated by the results of this study. MAGI2-AS3 inhibited the proliferation, migration, and invasion of LSCC cells in vitro and in vivo . Furthermore, the hypermethylation level of the MAGI2-AS3 promoter region was indicated by bisulfite genomic sequencing and methylation-specific polymerase chain reaction, such that MAGI2-AS3 expression was downregulated. Besides, MAGI2-AS3 promoter hypermethylation was regulated by DNA methyltransferase 1 (DNMT1), and MAGI2-AS3 expression was reversed by 5-Aza-2′-deoxycytidine (5-Aza). Moreover, the result of the RNA pull-down experiment suggested that 38 proteins were enriched in the MAGI2-AS3 group versus the control group in TU177 cells. To be specific, SPT6 (ie, a conserved protein) was enriched by fold change >10. SPT6 knockdown reduced the antitumor effect of MAGI2-AS3 in TU177 and AMC-HN-8 cells. Meanwhile, SPT6 overexpression inhibited the proliferation, metastasis, and invasion of TU177 and AMC-HN-8 cells. As revealed by the above findings, DNMT1-regulated MAGI2-AS3 promoter hypermethylation led to downregulated MAGI2-AS3 expression, such that the presence and progression of LSCC were inhibited in an SPT6 binding-dependent manner. |
| first_indexed | 2024-04-10T06:39:12Z |
| format | Article |
| id | doaj.art-0a505466c54846e898822e56f84fd5a8 |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-04-10T06:39:12Z |
| publishDate | 2023-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-0a505466c54846e898822e56f84fd5a82023-02-28T15:33:36ZengSAGE PublishingCell Transplantation1555-38922023-02-013210.1177/09636897231154574Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6Jiantao Wang0Chuan Yang1Huan Cao2Jianwang Yang3Wenxia Meng4Miaomiao Yu5Lei Yu6Baoshan Wang7Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaLong noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung cancer. However, the functions of MAGI2-AS3 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, MAGI2-AS3 expression level in LSCC tissue and cell lines was detected, and the effect of MAGI2-AS3 overexpressed on LSCC phenotypes and the possible influence mechanisms were examined. MAGI2-AS3 was downregulated in the tissues of LSCC patients versus non-tumor tissues, and it was correlated with advanced TNM (tumor, node, metastasis) stage and lymph node metastases, as indicated by the results of this study. MAGI2-AS3 inhibited the proliferation, migration, and invasion of LSCC cells in vitro and in vivo . Furthermore, the hypermethylation level of the MAGI2-AS3 promoter region was indicated by bisulfite genomic sequencing and methylation-specific polymerase chain reaction, such that MAGI2-AS3 expression was downregulated. Besides, MAGI2-AS3 promoter hypermethylation was regulated by DNA methyltransferase 1 (DNMT1), and MAGI2-AS3 expression was reversed by 5-Aza-2′-deoxycytidine (5-Aza). Moreover, the result of the RNA pull-down experiment suggested that 38 proteins were enriched in the MAGI2-AS3 group versus the control group in TU177 cells. To be specific, SPT6 (ie, a conserved protein) was enriched by fold change >10. SPT6 knockdown reduced the antitumor effect of MAGI2-AS3 in TU177 and AMC-HN-8 cells. Meanwhile, SPT6 overexpression inhibited the proliferation, metastasis, and invasion of TU177 and AMC-HN-8 cells. As revealed by the above findings, DNMT1-regulated MAGI2-AS3 promoter hypermethylation led to downregulated MAGI2-AS3 expression, such that the presence and progression of LSCC were inhibited in an SPT6 binding-dependent manner.https://doi.org/10.1177/09636897231154574 |
| spellingShingle | Jiantao Wang Chuan Yang Huan Cao Jianwang Yang Wenxia Meng Miaomiao Yu Lei Yu Baoshan Wang Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6 Cell Transplantation |
| title | Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6 |
| title_full | Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6 |
| title_fullStr | Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6 |
| title_full_unstemmed | Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6 |
| title_short | Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6 |
| title_sort | hypermethylation mediated lncrna magi2 as3 downregulation facilitates malignant progression of laryngeal squamous cell carcinoma via interacting with spt6 |
| url | https://doi.org/10.1177/09636897231154574 |
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