A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth

• Material Type: 博士論文
• ISSN: 1471-2407
• Title: A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth
• Volume: 19
• Author/Editor: Saijo, Saki; Kuwano, Yuki; Tange, Shoichiro; Rokutan, Kazuhito; Nishida, Kensei
• Author Heading: Saijo, Saki; Kuwano, Yuki; Tange, Shoichiro; Rokutan, Kazuhito; Nishida, Kensei
• Publication, Distribution, etc.: BioMed Central
• Publication Date: 2019-06-03
• Publication Date (W3CDTF): 2019-06-03
• Alternative Title: HOXA6-HOXA5遺伝子座の新規長鎖ノンコーディングRNAは大腸癌細胞の増殖を促進する
• Periodical title: BMC cancer
• Degree grantor/type: 徳島大学
• Date Granted: 2019-03-22
• Date Granted (W3CDTF): 2019-03-22
• Dissertation Number: 甲第3263号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3263号
• Text Language Code: eng
• Subject Heading: HOXA5; non-coding RNA; cell proliferation; colon cancer; epidermal growth factor signaling
• Target Audience: 一般
• Note (General): Background : Homeobox A5 (HOXA5), a member of the HOX family, plays an important role in tumor development and morphogenesis, although opposite effects on tumorigenesis have been observed, depending on the tissue type. In this study, we aimed to investigate the role of a novel transcript from the HOXA6-HOXA5 locus in colon cancer tumorigenesis.Methods : Human colon cancer cell lines were analyzed using next generation sequencing-based targeted mRNA capture. The effects of overexpression and silencing of HOXA5 transcripts were evaluated in vitro and using a xenograft nude mouse model.Results : We identified three novel transcripts (HOXA5 short, long 1, and long 2) transcribed from the HOXA6-HOXA5 locus in HCT116 colon cancer cells using next generation sequencing-based targeted mRNA capture. Knockdown of HOXA5 long 1 and long 2 transcripts did not affect cell growth, while selective silencing of HOXA5 short RNA inhibited cell growth independent of HOXA5 expression. Stable overexpression of HOXA5 short RNA promoted proliferation and migration of colon cancer cell lines HCT116, DLD1, and HT-29 and accelerated tumor growth in the xenograft mouse model. In vitro translation assays suggested HOXA5 short RNA was a functional long non-coding RNA (lncRNA). Consistent with these observations, expression of HOXA5 short RNA was upregulated in advanced colon cancer tissues. Ingenuity Pathway Analysis of differentially expressed genes between HOXA5 short RNA overexpressed and silenced HCT116 cells revealed that HOXA5 short RNA preferentially modified expression of epidermal growth factor (EGF) signal-related genes. Western blot analysis demonstrated that stable overexpression of HOXA5 short RNA increased EGF receptor levels and facilitated its phosphorylation in both HCT116 cells and xenograft tumors.Conclusions : Our results suggested that HOXA5 short RNA, a novel lncRNA, may play a crucial role in colon tumor growth through activation of EGF signaling.
• DOI: info:doi/10.1186/s12885-019-5715-0; https://doi.org/info:doi/10.1186/s12885-019-5715-0
• Persistent ID (NDL): info:ndljp/pid/11344404; https://dl.ndl.go.jp/pid/11344404
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2019-09-04T09:14:56+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/113406
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp