Senescence-related circRNA circHIF-1α is associated with pancreatic cancer progression
Abstract Recently, there has been growing interest in the role of circular RNAs (circRNAs) in the progression of human cancers. Cellular senescence, a known anti-tumour mechanism, has been observed in several types of cancer. However, the regulatory interplay of circRNAs with cellular senescence in...
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BMC
2025-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03645-w |
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| author | Hao Hua Yazu Deng Dijie Zheng Changhao Wu Liwen Chen Binbin Shi Zhiwei He Chao Yu |
| author_facet | Hao Hua Yazu Deng Dijie Zheng Changhao Wu Liwen Chen Binbin Shi Zhiwei He Chao Yu |
| author_sort | Hao Hua |
| collection | DOAJ |
| description | Abstract Recently, there has been growing interest in the role of circular RNAs (circRNAs) in the progression of human cancers. Cellular senescence, a known anti-tumour mechanism, has been observed in several types of cancer. However, the regulatory interplay of circRNAs with cellular senescence in pancreatic cancer (PC) is still unknown. Therefore, we identified circHIF-1α, hsa_circ_0007976, which was downregulated in senescent cells using circRNA microarray analysis. Meanwhile, significantly upregulated expression of circHIF-1α in pancreatic cancer tissue detected by reverse transcription-polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH). High circHIF-1α expression levels were found to independently predict poor survival outcomes. Subsequent treatments with DOX and H2O2 resulted in significantly lower levels of circHIF-1α. CircHIF-1α knockdown induces cellular senescence and suppresses PC proliferation in vitro experiments. The ability of circHIF-1α knockdown to suppress the progression of PC cells was further confirmed in vivo experiments. Our results showed that circHIF-1α is mainly presented in the nucleus of PC cells, also in the cytoplasm. Mechanistically, circHIF-1α inhibited senescence and accelerated the progression of PC cells through miR-375 sponging, thereby promoting HIF-1α expression levels. Nuclear circHIF-1α interacted with human antigen R protein (HUR) to increase HIF-1α expression. Thus, our results demonstrated that circHIF-1α ameliorates senescence and exacerbates growth in PC cells by increasing HIF-1α through targeting miR-375 and HUR, suggesting that targeting circHIF-1α offers a potential therapeutic candidate for PC. |
| format | Article |
| id | doaj-art-c2488856669d46cab6e703b0fcf966bf |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-c2488856669d46cab6e703b0fcf966bf2025-01-19T12:39:32ZengBMCCancer Cell International1475-28672025-01-0125111910.1186/s12935-025-03645-wSenescence-related circRNA circHIF-1α is associated with pancreatic cancer progressionHao Hua0Yazu Deng1Dijie Zheng2Changhao Wu3Liwen Chen4Binbin Shi5Zhiwei He6Chao Yu7School of Clinical Medicine, Guizhou Medical UniversitySchool of Clinical Medicine, Guizhou Medical UniversitySchool of Clinical Medicine, Guizhou Medical UniversitySchool of Clinical Medicine, Guizhou Medical UniversitySchool of Clinical Medicine, Guizhou Medical UniversitySchool of Clinical Medicine, Guizhou Medical UniversitySchool of Clinical Medicine, Guizhou Medical UniversitySchool of Clinical Medicine, Guizhou Medical UniversityAbstract Recently, there has been growing interest in the role of circular RNAs (circRNAs) in the progression of human cancers. Cellular senescence, a known anti-tumour mechanism, has been observed in several types of cancer. However, the regulatory interplay of circRNAs with cellular senescence in pancreatic cancer (PC) is still unknown. Therefore, we identified circHIF-1α, hsa_circ_0007976, which was downregulated in senescent cells using circRNA microarray analysis. Meanwhile, significantly upregulated expression of circHIF-1α in pancreatic cancer tissue detected by reverse transcription-polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH). High circHIF-1α expression levels were found to independently predict poor survival outcomes. Subsequent treatments with DOX and H2O2 resulted in significantly lower levels of circHIF-1α. CircHIF-1α knockdown induces cellular senescence and suppresses PC proliferation in vitro experiments. The ability of circHIF-1α knockdown to suppress the progression of PC cells was further confirmed in vivo experiments. Our results showed that circHIF-1α is mainly presented in the nucleus of PC cells, also in the cytoplasm. Mechanistically, circHIF-1α inhibited senescence and accelerated the progression of PC cells through miR-375 sponging, thereby promoting HIF-1α expression levels. Nuclear circHIF-1α interacted with human antigen R protein (HUR) to increase HIF-1α expression. Thus, our results demonstrated that circHIF-1α ameliorates senescence and exacerbates growth in PC cells by increasing HIF-1α through targeting miR-375 and HUR, suggesting that targeting circHIF-1α offers a potential therapeutic candidate for PC.https://doi.org/10.1186/s12935-025-03645-wPancreatic cancercircHIF-1αSenescenceHIF-1αHUR |
| spellingShingle | Hao Hua Yazu Deng Dijie Zheng Changhao Wu Liwen Chen Binbin Shi Zhiwei He Chao Yu Senescence-related circRNA circHIF-1α is associated with pancreatic cancer progression Cancer Cell International Pancreatic cancer circHIF-1α Senescence HIF-1α HUR |
| title | Senescence-related circRNA circHIF-1α is associated with pancreatic cancer progression |
| title_full | Senescence-related circRNA circHIF-1α is associated with pancreatic cancer progression |
| title_fullStr | Senescence-related circRNA circHIF-1α is associated with pancreatic cancer progression |
| title_full_unstemmed | Senescence-related circRNA circHIF-1α is associated with pancreatic cancer progression |
| title_short | Senescence-related circRNA circHIF-1α is associated with pancreatic cancer progression |
| title_sort | senescence related circrna circhif 1α is associated with pancreatic cancer progression |
| topic | Pancreatic cancer circHIF-1α Senescence HIF-1α HUR |
| url | https://doi.org/10.1186/s12935-025-03645-w |
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