RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3
Abstract Background RP11-296E3.2 is a novel long noncoding RNA (lncRNA) associated with colorectal cancer (CRC) metastasis, that was reported in our previous clinical studies. However, the mechanisms of RP11-296E3.2 in colorectal tumorigenesis remain elusive. Methods RNA sequencing (RNA-seq), Fluore...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04267-4 |
| _version_ | 1797789592668078080 |
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| author | Qian Shi Ying He Shouyu He Jingjing Li Ji Xia Tianwei Chen Lixia Huo Yuhang Ling Qinchen Liu Wei Zang Qiang Wang Chengwu Tang Xiang Wang |
| author_facet | Qian Shi Ying He Shouyu He Jingjing Li Ji Xia Tianwei Chen Lixia Huo Yuhang Ling Qinchen Liu Wei Zang Qiang Wang Chengwu Tang Xiang Wang |
| author_sort | Qian Shi |
| collection | DOAJ |
| description | Abstract Background RP11-296E3.2 is a novel long noncoding RNA (lncRNA) associated with colorectal cancer (CRC) metastasis, that was reported in our previous clinical studies. However, the mechanisms of RP11-296E3.2 in colorectal tumorigenesis remain elusive. Methods RNA sequencing (RNA-seq), Fluorescence in situ hybridization (FISH), Transwell assays and others, were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vitro. In situ and metastatic tumor models were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vivo. RNA-pulldown, RNA-interacting protein immunoprecipitation (RIP), tissue microarray (TMA) assay, a luciferase reporter assay, chromatin immunoprecipitation (ChIP) and others were performed to explore the mechanisms by which RP11-296E3.2 regulates CRC tumorigenesis. Results RP11-296E3.2 was confirmed to be associated with CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, RP11-296E3.2 directly bound to recombinant Y-Box Binding Protein 1 (YBX1) and enhanced signal transducer and activator of transcription 3 (STAT3) transcription and phosphorylation. YBX1 promoted the CRC cell proliferation and migration, while knockdown of RP11-296E3.2 attenuated the effects of YBX1 on CRC cell proliferation, and metastasis and the expression of several related downstream genes. We are the first to discover and confirm the existence of the YBX1/STAT3 pathway, a pathway dependent on RP11-296E3.2. Conclusion Together, these novel findings show that the RP11-296E3.2/YBX1 pathway promotes colorectal tumorigenesis and progression by activating STAT3 transcription and phosphorylation, and suggest that RP11-296E3.2 is a potential diagnostic biomarker and therapeutic target in CRC. |
| first_indexed | 2024-03-13T01:52:52Z |
| format | Article |
| id | doaj.art-cb30ed988af34cb6b3cce50d90e6c603 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-13T01:52:52Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-cb30ed988af34cb6b3cce50d90e6c6032023-07-02T11:25:41ZengBMCJournal of Translational Medicine1479-58762023-06-0121111810.1186/s12967-023-04267-4RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3Qian Shi0Ying He1Shouyu He2Jingjing Li3Ji Xia4Tianwei Chen5Lixia Huo6Yuhang Ling7Qinchen Liu8Wei Zang9Qiang Wang10Chengwu Tang11Xiang Wang12Key Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou UniversityKey Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou UniversityKey Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou UniversityKey Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of MedicineKey Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou UniversityKey Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou UniversityDepartment of General Surgery, Shanghai Fengxian Central Hospital (Affiliated Fengxian Hospital to Southern Medical University)Department of General Surgery, Shanghai Fengxian Central Hospital (Affiliated Fengxian Hospital to Southern Medical University)Medical Transformation Research Institute, The First Affiliated Hospital of Anhui Medical UniversityKey Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou UniversityKey Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou UniversityAbstract Background RP11-296E3.2 is a novel long noncoding RNA (lncRNA) associated with colorectal cancer (CRC) metastasis, that was reported in our previous clinical studies. However, the mechanisms of RP11-296E3.2 in colorectal tumorigenesis remain elusive. Methods RNA sequencing (RNA-seq), Fluorescence in situ hybridization (FISH), Transwell assays and others, were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vitro. In situ and metastatic tumor models were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vivo. RNA-pulldown, RNA-interacting protein immunoprecipitation (RIP), tissue microarray (TMA) assay, a luciferase reporter assay, chromatin immunoprecipitation (ChIP) and others were performed to explore the mechanisms by which RP11-296E3.2 regulates CRC tumorigenesis. Results RP11-296E3.2 was confirmed to be associated with CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, RP11-296E3.2 directly bound to recombinant Y-Box Binding Protein 1 (YBX1) and enhanced signal transducer and activator of transcription 3 (STAT3) transcription and phosphorylation. YBX1 promoted the CRC cell proliferation and migration, while knockdown of RP11-296E3.2 attenuated the effects of YBX1 on CRC cell proliferation, and metastasis and the expression of several related downstream genes. We are the first to discover and confirm the existence of the YBX1/STAT3 pathway, a pathway dependent on RP11-296E3.2. Conclusion Together, these novel findings show that the RP11-296E3.2/YBX1 pathway promotes colorectal tumorigenesis and progression by activating STAT3 transcription and phosphorylation, and suggest that RP11-296E3.2 is a potential diagnostic biomarker and therapeutic target in CRC.https://doi.org/10.1186/s12967-023-04267-4CRCMetastasisProliferationRP11-296E3.2/YBX1STAT3 transcription |
| spellingShingle | Qian Shi Ying He Shouyu He Jingjing Li Ji Xia Tianwei Chen Lixia Huo Yuhang Ling Qinchen Liu Wei Zang Qiang Wang Chengwu Tang Xiang Wang RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3 Journal of Translational Medicine CRC Metastasis Proliferation RP11-296E3.2/YBX1 STAT3 transcription |
| title | RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3 |
| title_full | RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3 |
| title_fullStr | RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3 |
| title_full_unstemmed | RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3 |
| title_short | RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3 |
| title_sort | rp11 296e3 2 acts as an important molecular chaperone for ybx1 and promotes colorectal cancer proliferation and metastasis by activating stat3 |
| topic | CRC Metastasis Proliferation RP11-296E3.2/YBX1 STAT3 transcription |
| url | https://doi.org/10.1186/s12967-023-04267-4 |
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