{"_buckets": {"deposit": "3b6f7f1c-ce0b-4c83-a33b-b77a8ec646e4"}, "_deposit": {"id": "32142", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "32142"}, "status": "published"}, "_oai": {"id": "oai:niigata-u.repo.nii.ac.jp:00032142", "sets": ["455", "564"]}, "item_6_alternative_title_1": {"attribute_name": "その他のタイトル", "attribute_value_mlt": [{"subitem_alternative_title": "腫瘍形成におけるケモカインCXCL12を標的とするマイクロRNA-342の機能的役割の研究"}]}, "item_6_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2019-03-25", "bibliographicIssueDateType": "Issued"}, "bibliographicPageEnd": "68", "bibliographicPageStart": "1", "bibliographic_titles": [{}]}]}, "item_6_date_granted_51": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2019-03-25"}]}, "item_6_degree_grantor_49": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_name": "新潟大学"}]}]}, "item_6_degree_name_48": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士（理学）"}]}, "item_6_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "　A neoplasm or tumor is a group of cells that have undergone unregulated growth and frequently form a mass or lump. The past decades, numerous molecular biology mechanisms have been uncovered to seek an understanding in tumor, such as, growth pathways, cell cycle, cell apoptosis, angiogenesis, cancer stem cells and more recently exosome-mediated molecules’ transportation, and targeted immunotherapy. However, much work remains to do toward understanding the mechanistic underpinnings of each hallmarks. \n　MicroRNAs (miRNAs), a classical ~22 nucleotides noncoding RNAs, are post-transcriptional regulators of protein-coding gene expression. The regulatory role of miRNAs makes it an important player in tumor development process: initiation, development, progression and metastasis. \n　The sarcoma cell lines, MS-K and LM-8, are two commonly used models in search of gene candidates involved in tumorigenesis or angiogenesis in C3H mice. Tumors formed by MS-K cells grow faster, and showed more enriched blood vessels in contrast to LM-8 tumors. While, miRNAs expression analysis indicated that the MS-K expressed a lower level of miR-342 compared to that in the LM-8. The miR-342 has been reported as a tumor-suppressor or an oncogenesis related-miRNA based on functions or expression changes in multiple types of cancers, \n　Here, I provide evidence that miR-342 serves as a tumor suppressor via targeting chemokine CXCL12 (also known as Stroma Derived Factor-1alpha; SDF-1α). Stable overexpression of miR-342 in MS-K cells inhibited cell proliferation, and capacity of colony formation in vitro. Moreover, induced miR-342 promoted cell cycle arrest in the G0/G1 phase and cell apoptosis. Bioinformatics analysis indicated chemokine CXCL12 mRNA was a putative target of miR-342. RT-PCR and western blotting analysis revealed a reversely correlation between endogenous CXCL12 expression and mature miR-342 RNA levels in MS-K and/or LM-8. Dual-luciferase reporter assay experiments validated the interaction between miR-342 and CXCL12 3’-UTR. \n　The chemokine CXCL12 is a well studied α-chemokine that binds to receptors CXCR4/7, and has been implicated in the recruitment of monocytes / macrophages and tumorigenesis. In vivo experiments, overexpression of miR-342 significantly suppressed MS-K tumor growth. More importantly, more CD11b-positive macrophages was accumulated in tumors formed by MS-K-miR-342 cells, either in total number of CD11b-positive cells or proportion against total tumor cells, compared to controls. Furthermore, the expression of proangiogenic genes (Vegf-A and Thbs1) and M2-subtype macrophage markers (Cd163, Dectin1 and Ym1) was significantly decreased in the CD11b-positive cells derived from MS-K-miR-342 tumors compared to controls. In addition, down-regulated level of Cxcl12 and its receptor Cxcr4 was also observed, but the miR-342 level was not markedly affected in the CD11b-positve cells from MS-K-miR-342 tumors in contrast to controls. These results implying that the miR-342 derived from MS-K-miR-342 cells but not endogenous miR-342, might be contribute to Cxcl12 suppression in tumor-infiltrated macrophages. Finally, restored CXCL12 expression in MS-K-miR-342 cells rescued cell proliferation, and cell cycle arrest in vitro. \n　Together, these studies demonstrate that miR-342 is involved in MS-K tumor growth as a tumor-suppressor by targeting chemokine CXCL12.", "subitem_description_type": "Abstract"}]}, "item_6_description_5": {"attribute_name": "内容記述", "attribute_value_mlt": [{"subitem_description": "学位の種類: 博士（理学）. 報告番号: 甲第4607号. 学位記番号: 新大院博（理）甲第440号. 学位授与年月日: 平成31年3月25日", "subitem_description_type": "Other"}]}, "item_6_description_53": {"attribute_name": "学位記番号", "attribute_value_mlt": [{"subitem_description": "新大院博（理）甲第440号", "subitem_description_type": "Other"}]}, "item_6_dissertation_number_52": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "13101甲第4607号"}]}, "item_6_publisher_7": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "新潟大学"}]}, "item_6_select_19": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "ETD"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Tian, Yijun"}], "nameIdentifiers": [{"nameIdentifier": "175282", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-09-10"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "h30fsk440.pdf", "filesize": [{"value": "2.3 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 2300000.0, "url": {"label": "本文", "url": "https://niigata-u.repo.nii.ac.jp/record/32142/files/h30fsk440.pdf"}, "version_id": "687fa2a3-9b07-4511-b3e3-23b55c9cbafb"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-09-10"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "h30fsk440_a.pdf", "filesize": [{"value": "208.1 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 208100.0, "url": {"label": "要旨", "url": "https://niigata-u.repo.nii.ac.jp/record/32142/files/h30fsk440_a.pdf"}, "version_id": "7cf44bbf-bd31-4b8e-ad57-e023cf28d806"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "thesis", "resourceuri": "http://purl.org/coar/resource_type/c_46ec"}]}, "item_title": "Study on Functional Roles of MicroRNA-342 via Targeting Chemokine CXCL12 in Tumorigenesis", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Study on Functional Roles of MicroRNA-342 via Targeting Chemokine CXCL12 in Tumorigenesis"}, {"subitem_title": "Study on Functional Roles of MicroRNA-342 via Targeting Chemokine CXCL12 in Tumorigenesis", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["455", "564"], "permalink_uri": "http://hdl.handle.net/10191/51330", "pubdate": {"attribute_name": "公開日", "attribute_value": "2019-07-09"}, "publish_date": "2019-07-09", "publish_status": "0", "recid": "32142", "relation": {}, "relation_version_is_last": true, "title": ["Study on Functional Roles of MicroRNA-342 via Targeting Chemokine CXCL12 in Tumorigenesis"], "weko_shared_id": 2}