A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability
Abstract Metastasis is the leading cause of cancer-related death, where TGFβ-induced epithelial-mesenchymal transition (EMT) process confers on cancer cells increased metastatic potential. However, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42571-1 |
| _version_ | 1797647261424943104 |
|---|---|
| author | Ke Li Jiawei Guo Yue Ming Shuang Chen Tingting Zhang Hulin Ma Xin Fu Jin Wang Wenrong Liu Yong Peng |
| author_facet | Ke Li Jiawei Guo Yue Ming Shuang Chen Tingting Zhang Hulin Ma Xin Fu Jin Wang Wenrong Liu Yong Peng |
| author_sort | Ke Li |
| collection | DOAJ |
| description | Abstract Metastasis is the leading cause of cancer-related death, where TGFβ-induced epithelial-mesenchymal transition (EMT) process confers on cancer cells increased metastatic potential. However, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA called circITGB6 as an indispensable factor during the TGFβ-mediated EMT process. circITGB6 is significantly upregulated in metastatic cancer samples and its higher abundance is closely correlated to worse prognosis of colorectal cancer (CRC) patients. Through gain- and loss-of-function assays, circITGB6 is found to potently promote EMT process and tumor metastasis in various models in vitro and in vivo. Mechanistically, circITGB6 enhances the mRNA stability of PDPN, an EMT-promoting gene, by directly interacting with IGF2BP3. Notably, interfering circITGB6 with PEI-coated specific siRNA effectively represses liver metastasis. Therefore, our study reveals the function of a TGFβ-regulated circRNA in tumor metastasis and suggests that targeting circITGB6 is a promising strategy for cancer therapy. |
| first_indexed | 2024-03-11T15:13:45Z |
| format | Article |
| id | doaj.art-61752a8863d548acbdcd9b741ee52c55 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T15:13:45Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-61752a8863d548acbdcd9b741ee52c552023-10-29T12:28:18ZengNature PortfolioNature Communications2041-17232023-10-0114111810.1038/s41467-023-42571-1A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stabilityKe Li0Jiawei Guo1Yue Ming2Shuang Chen3Tingting Zhang4Hulin Ma5Xin Fu6Jin Wang7Wenrong Liu8Yong Peng9Laboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityAbstract Metastasis is the leading cause of cancer-related death, where TGFβ-induced epithelial-mesenchymal transition (EMT) process confers on cancer cells increased metastatic potential. However, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA called circITGB6 as an indispensable factor during the TGFβ-mediated EMT process. circITGB6 is significantly upregulated in metastatic cancer samples and its higher abundance is closely correlated to worse prognosis of colorectal cancer (CRC) patients. Through gain- and loss-of-function assays, circITGB6 is found to potently promote EMT process and tumor metastasis in various models in vitro and in vivo. Mechanistically, circITGB6 enhances the mRNA stability of PDPN, an EMT-promoting gene, by directly interacting with IGF2BP3. Notably, interfering circITGB6 with PEI-coated specific siRNA effectively represses liver metastasis. Therefore, our study reveals the function of a TGFβ-regulated circRNA in tumor metastasis and suggests that targeting circITGB6 is a promising strategy for cancer therapy.https://doi.org/10.1038/s41467-023-42571-1 |
| spellingShingle | Ke Li Jiawei Guo Yue Ming Shuang Chen Tingting Zhang Hulin Ma Xin Fu Jin Wang Wenrong Liu Yong Peng A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability Nature Communications |
| title | A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability |
| title_full | A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability |
| title_fullStr | A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability |
| title_full_unstemmed | A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability |
| title_short | A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability |
| title_sort | circular rna activated by tgfβ promotes tumor metastasis through enhancing igf2bp3 mediated pdpn mrna stability |
| url | https://doi.org/10.1038/s41467-023-42571-1 |
| work_keys_str_mv | AT keli acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT jiaweiguo acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT yueming acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT shuangchen acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT tingtingzhang acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT hulinma acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT xinfu acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT jinwang acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT wenrongliu acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT yongpeng acircularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT keli circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT jiaweiguo circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT yueming circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT shuangchen circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT tingtingzhang circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT hulinma circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT xinfu circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT jinwang circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT wenrongliu circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability AT yongpeng circularrnaactivatedbytgfbpromotestumormetastasisthroughenhancingigf2bp3mediatedpdpnmrnastability |