OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis.
OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis.
复制标题
OLA1 通过激活 HIF1α/CA9 轴促进结直肠癌肿瘤发生
DOI：
10.1186/s12885-022-09508-1
复制
发表时间：
2022-04-19
期刊：
影响因子：
3.8
通讯作者：
Xu, Dong
中科院分区：
文献类型：
--
作者：
Liu, Yue;Kong, Xiang-Xing;He, Jin-Jie;Xu, Yan-Bo;Zhang, Jian-Kun;Zou, Lu-Yang;Ding, Ke-Feng;Xu, Dong
obg样atp酶1 （OLA1）是一种高度保守的GTPase，在多种恶性肿瘤中过表达，但其在结直肠癌（CRC）中的作用研究较少。应用三个公共CRC基因数据库进行OLA1 mRNA表达检测。回顾性收集浙江大学第二附属医院（SAHZU） 111例结直肠癌患者的临床资料，进行OLA1蛋白表达和Kaplan-Meier生存分析。利用CRISPR-Cas9对OLA1稳定敲除的CRC细胞系进行体外和体内实验。与匹配的周围组织相比，OLA1在84%的结直肠癌中高表达。OLA1高表达患者的5年生存率（47%）明显低于OLA1低表达患者（75%）。OLA1高表达是结直肠癌患者预后不良的独立因素。OLA1-KO结直肠癌细胞系在体外和体内均表现出较低的生长和肿瘤发生能力。通过mRNA序列分析，我们在OLA1-KO细胞系中发现113个差异表达基因，其中63个与缺氧相关。HIF1α是缺氧调控的关键分子。进一步的分子机制显示，HIF1α /CA9 mRNA和/或蛋白水平在OLA1-KO细胞系中严重下调，这可以解释肿瘤发生受损。根据前人的研究，HIF1α是GSK3β的下游基因，我们证实了GSK3β在OLA1-KO细胞系中过度激活。OLA1是一个新的基因，通过激活HIF1α/CA9轴与CRC的癌变和不良预后相关，这可能由GSK3β解释。在线版本包含补充材料，可在10.1186/s12885-022-09508-1获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12885-022-09508-1.
登录
查看更多内容
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
5.3
作者：
Fluegel, Daniela;Goerlach, Agnes;Kietzmann, Thomas
通讯作者：
Kietzmann, Thomas
DOI：
10.1093/annonc/mdy085
发表时间：
2018-05-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Smeby J;Sveen A;Merok MA;Danielsen SA;Eilertsen IA;Guren MG;Dienstmann R;Nesbakken A;Lothe RA
通讯作者：
Lothe RA
影响因子：
4
作者：
Gradia, Daniela F.;Rau, Karlan;Fragoso, Stenio P.
通讯作者：
Fragoso, Stenio P.
影响因子：
3.3
作者：
Pollheimer, Marion J.;Kornprat, Peter;Langner, Cord
通讯作者：
Langner, Cord