OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis
Abstract Background Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied. Patients and methods Three public CRC gene databases were applied for OLA1 mRNA expression detection. The...
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| Format: | Article |
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BMC
2022-04-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-09508-1 |
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| author | Yue Liu Xiang-Xing Kong Jin-Jie He Yan-Bo Xu Jian-Kun Zhang Lu-Yang Zou Ke-Feng Ding Dong Xu |
| author_facet | Yue Liu Xiang-Xing Kong Jin-Jie He Yan-Bo Xu Jian-Kun Zhang Lu-Yang Zou Ke-Feng Ding Dong Xu |
| author_sort | Yue Liu |
| collection | DOAJ |
| description | Abstract Background Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied. Patients and methods Three public CRC gene databases were applied for OLA1 mRNA expression detection. The clinical data of 111 CRC patients were retrospectively collected from the Second Affiliated Hospital of Zhejiang University (SAHZU) for OLA1 protein expression and Kaplan-Meier Survival analysis. OLA1 stably knocked out CRC cell lines were conducted by CRISPR-Cas9 for experiments in vitro and in vivo. Results OLA1 was highly expressed in 84% CRC compared to matched surrounding tissues. Patients with OLA1 high expression had a significantly lower 5-year survival rate (47%) than those with OLA1 low expression (75%). OLA1 high expression was an independent factor of poor prognosis in CRC patients. OLA1-KO CRC cell lines showed lower ability of growth and tumorigenesis in vitro and in vivo. By mRNA sequence analysis, we found 113 differential express genes in OLA1-KO cell lines, of which 63 were hypoxic related. HIF1α was a key molecule in hypoxic regulation. Further molecular mechanisms showed HIF1α /CA9 mRNA and/or protein levels were heavily downregulated in OLA1-KO cell lines, which could explain the impaired tumorigenesis. According to previous studies, HIF1α was a downstream gene of GSK3β, we verified GSK3β was over-activated in OLA1-KO cell lines. Conclusion OLA1 was a new gene that was associated with carcinogenesis and poor outcomes in CRC by activation of HIF1α/CA9 axis, which may be interpreted by GSK3β. |
| first_indexed | 2024-04-14T00:38:05Z |
| format | Article |
| id | doaj.art-d0f7d2dc7f59492cad55d8993768d890 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-14T00:38:05Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-d0f7d2dc7f59492cad55d8993768d8902022-12-22T02:22:16ZengBMCBMC Cancer1471-24072022-04-0122111210.1186/s12885-022-09508-1OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axisYue Liu0Xiang-Xing Kong1Jin-Jie He2Yan-Bo Xu3Jian-Kun Zhang4Lu-Yang Zou5Ke-Feng Ding6Dong Xu7Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of MedicineKey Laboratory of Cancer Prevention and Intervention, Ministry of Education, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of MedicineKey Laboratory of Cancer Prevention and Intervention, Ministry of Education, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of MedicineKey Laboratory of Cancer Prevention and Intervention, Ministry of Education, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of MedicineKey Laboratory of Cancer Prevention and Intervention, Ministry of Education, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of MedicineKey Laboratory of Cancer Prevention and Intervention, Ministry of Education, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of MedicineKey Laboratory of Cancer Prevention and Intervention, Ministry of Education, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of MedicineKey Laboratory of Cancer Prevention and Intervention, Ministry of Education, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of MedicineAbstract Background Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied. Patients and methods Three public CRC gene databases were applied for OLA1 mRNA expression detection. The clinical data of 111 CRC patients were retrospectively collected from the Second Affiliated Hospital of Zhejiang University (SAHZU) for OLA1 protein expression and Kaplan-Meier Survival analysis. OLA1 stably knocked out CRC cell lines were conducted by CRISPR-Cas9 for experiments in vitro and in vivo. Results OLA1 was highly expressed in 84% CRC compared to matched surrounding tissues. Patients with OLA1 high expression had a significantly lower 5-year survival rate (47%) than those with OLA1 low expression (75%). OLA1 high expression was an independent factor of poor prognosis in CRC patients. OLA1-KO CRC cell lines showed lower ability of growth and tumorigenesis in vitro and in vivo. By mRNA sequence analysis, we found 113 differential express genes in OLA1-KO cell lines, of which 63 were hypoxic related. HIF1α was a key molecule in hypoxic regulation. Further molecular mechanisms showed HIF1α /CA9 mRNA and/or protein levels were heavily downregulated in OLA1-KO cell lines, which could explain the impaired tumorigenesis. According to previous studies, HIF1α was a downstream gene of GSK3β, we verified GSK3β was over-activated in OLA1-KO cell lines. Conclusion OLA1 was a new gene that was associated with carcinogenesis and poor outcomes in CRC by activation of HIF1α/CA9 axis, which may be interpreted by GSK3β.https://doi.org/10.1186/s12885-022-09508-1Colorectal cancerTumorigenesisOLA1HIF 1αCA9 |
| spellingShingle | Yue Liu Xiang-Xing Kong Jin-Jie He Yan-Bo Xu Jian-Kun Zhang Lu-Yang Zou Ke-Feng Ding Dong Xu OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis BMC Cancer Colorectal cancer Tumorigenesis OLA1 HIF 1α CA9 |
| title | OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis |
| title_full | OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis |
| title_fullStr | OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis |
| title_full_unstemmed | OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis |
| title_short | OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis |
| title_sort | ola1 promotes colorectal cancer tumorigenesis by activation of hif1α ca9 axis |
| topic | Colorectal cancer Tumorigenesis OLA1 HIF 1α CA9 |
| url | https://doi.org/10.1186/s12885-022-09508-1 |
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