CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive feedback loop
Abstract Antisense circular RNA is a special type of circular RNA that is derived from the antisense complementary strand of parental mRNA. However, the function of antisense circRNA in hepatocellular carcinoma (HCC) is still unclear. Here, we reported that CSF3R-AS was upregulated in HCC and correl...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-03-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07558-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850065629729521664 |
|---|---|
| author | Ziyang Feng Yan Gao Changjing Cai Jun Tan Ping Liu Yihong Chen Gongping Deng Yanhong Ouyang Xuewen Liu Ke Cao Shan Zeng Ying Han Xiangying Deng Hong Shen |
| author_facet | Ziyang Feng Yan Gao Changjing Cai Jun Tan Ping Liu Yihong Chen Gongping Deng Yanhong Ouyang Xuewen Liu Ke Cao Shan Zeng Ying Han Xiangying Deng Hong Shen |
| author_sort | Ziyang Feng |
| collection | DOAJ |
| description | Abstract Antisense circular RNA is a special type of circular RNA that is derived from the antisense complementary strand of parental mRNA. However, the function of antisense circRNA in hepatocellular carcinoma (HCC) is still unclear. Here, we reported that CSF3R-AS was upregulated in HCC and correlated with a poor prognosis. CSF3R-AS promoted the proliferation, angiogenesis, and metastasis of HCC, and inhibited apoptosis. Mechanistically, CSF3R-AS has a 180-base complementary pairing sequence with its parental mRNA CSF3R, which can directly bind to CSF3R and recruit RBMS3 to stabilize its parental mRNA, and finally activate JAK2/STAT3 signaling pathway. Interestingly, STAT3 can act as a transcription factor of CSF3R-AS, which means that there is a CSF3R-AS/CSF3R/JAK2/STAT3 positive feedback loop in HCC. Finally, the CSF3R-AS/CSF3R/JAK2/STAT3 positive feedback loop was also activated in HCC sorafenib-resistant cells, and blocking this loop was expected to improve the sensitivity of HCC to sorafenib. These findings suggested that the CSF3R-AS/CSF3R/JAK2/STAT3 positive feedback loop could promote HCC progression and sorafenib resistance. Blocking this loop is expected to provide new research directions and therapy targets for HCC. |
| format | Article |
| id | doaj-art-b0048639fac54f40ad3b77e18db3dcb9 |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-b0048639fac54f40ad3b77e18db3dcb92025-08-20T02:48:57ZengNature Publishing GroupCell Death and Disease2041-48892025-03-0116111210.1038/s41419-025-07558-4CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive feedback loopZiyang Feng0Yan Gao1Changjing Cai2Jun Tan3Ping Liu4Yihong Chen5Gongping Deng6Yanhong Ouyang7Xuewen Liu8Ke Cao9Shan Zeng10Ying Han11Xiangying Deng12Hong Shen13Department of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Emergency, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversityDepartment of Emergency, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversityDepartment of Oncology, The Third Xiangya Hospital, Central South UniversityDepartment of Oncology, The Third Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityAbstract Antisense circular RNA is a special type of circular RNA that is derived from the antisense complementary strand of parental mRNA. However, the function of antisense circRNA in hepatocellular carcinoma (HCC) is still unclear. Here, we reported that CSF3R-AS was upregulated in HCC and correlated with a poor prognosis. CSF3R-AS promoted the proliferation, angiogenesis, and metastasis of HCC, and inhibited apoptosis. Mechanistically, CSF3R-AS has a 180-base complementary pairing sequence with its parental mRNA CSF3R, which can directly bind to CSF3R and recruit RBMS3 to stabilize its parental mRNA, and finally activate JAK2/STAT3 signaling pathway. Interestingly, STAT3 can act as a transcription factor of CSF3R-AS, which means that there is a CSF3R-AS/CSF3R/JAK2/STAT3 positive feedback loop in HCC. Finally, the CSF3R-AS/CSF3R/JAK2/STAT3 positive feedback loop was also activated in HCC sorafenib-resistant cells, and blocking this loop was expected to improve the sensitivity of HCC to sorafenib. These findings suggested that the CSF3R-AS/CSF3R/JAK2/STAT3 positive feedback loop could promote HCC progression and sorafenib resistance. Blocking this loop is expected to provide new research directions and therapy targets for HCC.https://doi.org/10.1038/s41419-025-07558-4 |
| spellingShingle | Ziyang Feng Yan Gao Changjing Cai Jun Tan Ping Liu Yihong Chen Gongping Deng Yanhong Ouyang Xuewen Liu Ke Cao Shan Zeng Ying Han Xiangying Deng Hong Shen CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive feedback loop Cell Death and Disease |
| title | CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive feedback loop |
| title_full | CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive feedback loop |
| title_fullStr | CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive feedback loop |
| title_full_unstemmed | CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive feedback loop |
| title_short | CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive feedback loop |
| title_sort | csf3r as promotes hepatocellular carcinoma progression and sorafenib resistance through the csf3r jak2 stat3 positive feedback loop |
| url | https://doi.org/10.1038/s41419-025-07558-4 |
| work_keys_str_mv | AT ziyangfeng csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT yangao csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT changjingcai csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT juntan csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT pingliu csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT yihongchen csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT gongpingdeng csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT yanhongouyang csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT xuewenliu csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT kecao csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT shanzeng csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT yinghan csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT xiangyingdeng csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop AT hongshen csf3raspromoteshepatocellularcarcinomaprogressionandsorafenibresistancethroughthecsf3rjak2stat3positivefeedbackloop |