A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth
Abstract 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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-06-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-019-5715-0 |
| _version_ | 1818290566411059200 |
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| author | Saki Saijo Yuki Kuwano Shoichiro Tange Kazuhito Rokutan Kensei Nishida |
| author_facet | Saki Saijo Yuki Kuwano Shoichiro Tange Kazuhito Rokutan Kensei Nishida |
| author_sort | Saki Saijo |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T02:30:12Z |
| format | Article |
| id | doaj.art-67f639b2d01c48b186e6728233f72fbf |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T02:30:12Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-67f639b2d01c48b186e6728233f72fbf2022-12-22T00:02:31ZengBMCBMC Cancer1471-24072019-06-0119111410.1186/s12885-019-5715-0A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growthSaki Saijo0Yuki Kuwano1Shoichiro Tange2Kazuhito Rokutan3Kensei Nishida4Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate SchoolAbstract 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.http://link.springer.com/article/10.1186/s12885-019-5715-0HOXA5Non-coding RNACell proliferationColon cancerEpidermal growth factor signaling |
| spellingShingle | Saki Saijo Yuki Kuwano Shoichiro Tange Kazuhito Rokutan Kensei Nishida A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth BMC Cancer HOXA5 Non-coding RNA Cell proliferation Colon cancer Epidermal growth factor signaling |
| title | A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth |
| title_full | A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth |
| title_fullStr | A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth |
| title_full_unstemmed | A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth |
| title_short | A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth |
| title_sort | novel long non coding rna from the hoxa6 hoxa5 locus facilitates colon cancer cell growth |
| topic | HOXA5 Non-coding RNA Cell proliferation Colon cancer Epidermal growth factor signaling |
| url | http://link.springer.com/article/10.1186/s12885-019-5715-0 |
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