LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL‐6–STAT3 pathway
Long noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer. There is a comparable number of lncRNAs to protein‐coding genes, but the expression patterns, functions, and molecular mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. In this study, we report the ident...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-11-01
|
| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12538 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846159292928884736 |
|---|---|
| author | Jiaxing Wang Junfeng Zhou Caiyun Jiang Jing Zheng Hiroki Namba Pan Chi Tetsuya Asakawa |
| author_facet | Jiaxing Wang Junfeng Zhou Caiyun Jiang Jing Zheng Hiroki Namba Pan Chi Tetsuya Asakawa |
| author_sort | Jiaxing Wang |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer. There is a comparable number of lncRNAs to protein‐coding genes, but the expression patterns, functions, and molecular mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. In this study, we report the identification of a novel lncRNA, named long noncoding RNA regulating IL‐6 transcription (LNRRIL6), which is upregulated in CRC tissues and cell lines. Increased LNRRIL6 expression is associated with aggressive clinicopathological characteristics and poor prognosis of CRC patients. Functional experiments showed that enhanced expression of LNRRIL6 promotes CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Conversely, depletion of LNRRIL6 inhibits CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Mechanistically, we revealed that LNRRIL6 physically binds to the IL‐6 promoter, thereby increasing IL‐6 transcription, inducing IL‐6 autocrine signaling, and activating the IL‐6/STAT3 pathway. The expression of IL‐6 is positively associated with that of LNRRIL6 in CRC tissues. Blocking the IL‐6/STAT3 pathway using the FDA‐approved IL‐6‐receptor antagonist antibody, tocilizumab, abolished the oncogenic role of LNRRIL6 in CRC. Taken together, these findings identify a novel lncRNA, LNRRIL6, that promotes CRC cell survival through activation of the IL‐6/STAT3 pathway and suggest that LNRRIL6 may be a potential prognostic biomarker and therapeutic target for CRC. |
| format | Article |
| id | doaj-art-1d97559a9acd4f3c9229d56e6bea852d |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2019-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-1d97559a9acd4f3c9229d56e6bea852d2024-11-23T12:01:00ZengWileyMolecular Oncology1574-78911878-02612019-11-0113112344236010.1002/1878-0261.12538LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL‐6–STAT3 pathwayJiaxing Wang0Junfeng Zhou1Caiyun Jiang2Jing Zheng3Hiroki Namba4Pan Chi5Tetsuya Asakawa6Department of Gastrointestinal Surgery The First Affiliated Hospital of Fujian Medical University Fuzhou ChinaDepartment of Gastrointestinal Surgery The First Affiliated Hospital of Fujian Medical University Fuzhou ChinaDepartment of Colorectal Surgery Fujian Medical University Union Hospital Fuzhou ChinaFujian Institute of Hematology Fujian Provincial Key Laboratory on Hematology Fujian Medical University Union Hospital Fuzhou ChinaDepartment of Neurosurgery Hamamatsu University School of Medicine Hamamatsu JapanDepartment of Colorectal Surgery Fujian Medical University Union Hospital Fuzhou ChinaDepartment of Neurosurgery Hamamatsu University School of Medicine Hamamatsu JapanLong noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer. There is a comparable number of lncRNAs to protein‐coding genes, but the expression patterns, functions, and molecular mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. In this study, we report the identification of a novel lncRNA, named long noncoding RNA regulating IL‐6 transcription (LNRRIL6), which is upregulated in CRC tissues and cell lines. Increased LNRRIL6 expression is associated with aggressive clinicopathological characteristics and poor prognosis of CRC patients. Functional experiments showed that enhanced expression of LNRRIL6 promotes CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Conversely, depletion of LNRRIL6 inhibits CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Mechanistically, we revealed that LNRRIL6 physically binds to the IL‐6 promoter, thereby increasing IL‐6 transcription, inducing IL‐6 autocrine signaling, and activating the IL‐6/STAT3 pathway. The expression of IL‐6 is positively associated with that of LNRRIL6 in CRC tissues. Blocking the IL‐6/STAT3 pathway using the FDA‐approved IL‐6‐receptor antagonist antibody, tocilizumab, abolished the oncogenic role of LNRRIL6 in CRC. Taken together, these findings identify a novel lncRNA, LNRRIL6, that promotes CRC cell survival through activation of the IL‐6/STAT3 pathway and suggest that LNRRIL6 may be a potential prognostic biomarker and therapeutic target for CRC.https://doi.org/10.1002/1878-0261.12538colorectal cancerIL‐6IL‐6−STAT3 pathwayLNRRIL6long noncoding RNA |
| spellingShingle | Jiaxing Wang Junfeng Zhou Caiyun Jiang Jing Zheng Hiroki Namba Pan Chi Tetsuya Asakawa LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL‐6–STAT3 pathway Molecular Oncology colorectal cancer IL‐6 IL‐6−STAT3 pathway LNRRIL6 long noncoding RNA |
| title | LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL‐6–STAT3 pathway |
| title_full | LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL‐6–STAT3 pathway |
| title_fullStr | LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL‐6–STAT3 pathway |
| title_full_unstemmed | LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL‐6–STAT3 pathway |
| title_short | LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL‐6–STAT3 pathway |
| title_sort | lnrril6 a novel long noncoding rna protects colorectal cancer cells by activating the il 6 stat3 pathway |
| topic | colorectal cancer IL‐6 IL‐6−STAT3 pathway LNRRIL6 long noncoding RNA |
| url | https://doi.org/10.1002/1878-0261.12538 |
| work_keys_str_mv | AT jiaxingwang lnrril6anovellongnoncodingrnaprotectscolorectalcancercellsbyactivatingtheil6stat3pathway AT junfengzhou lnrril6anovellongnoncodingrnaprotectscolorectalcancercellsbyactivatingtheil6stat3pathway AT caiyunjiang lnrril6anovellongnoncodingrnaprotectscolorectalcancercellsbyactivatingtheil6stat3pathway AT jingzheng lnrril6anovellongnoncodingrnaprotectscolorectalcancercellsbyactivatingtheil6stat3pathway AT hirokinamba lnrril6anovellongnoncodingrnaprotectscolorectalcancercellsbyactivatingtheil6stat3pathway AT panchi lnrril6anovellongnoncodingrnaprotectscolorectalcancercellsbyactivatingtheil6stat3pathway AT tetsuyaasakawa lnrril6anovellongnoncodingrnaprotectscolorectalcancercellsbyactivatingtheil6stat3pathway |