Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
J Clin Lab Anal. 2020 Sep;34(9):e23405. doi: 10.1002/jcla.23405. Epub 2020 Jul 7.
hsa_circ_0000826 has been previously linked to CRC through the competing endogenous RNA network; however, the upstream driver of hsa_circ_0000826 elevation remains unknown. In this study, we aim to elucidate the effect of hypoxia-induced hsa_circ_0000826 on CRC tumorigenesis and metastasis.
RNA scope assay was used to evaluate the expression of hsa_circ_0000826 in CRC cells under hypoxia condition. The effects of hsa_circ_0000826 on phenotypes of CRC cells were evaluated through cell migration and invasion assay. The nude, AOM-DSS model mice and APC mice were used to investigate the relationship between circ_0000826, hypoxia, and CRC in mice. A total of 100 CRC tissue samples, as well as the paired adjacent tissues, were collected, and qRT-PCR assay was used to detect the expression of hsa_circ_0000826 in these samples.
Hypoxia-induced hsa_circ_0000826 overexpression can increase the malignant phenotypes, tumor formation, and metastasis capability of CRC cells in vitro. mmu_circ_0000826 levels were significantly increased in the CRC tissues from AOM-DSS and APC mice model under hypoxia conditions. Further, the hypoxia-induced upregulation of mmu_circ_0000826 can also promote CRC tumorigenesis and liver metastasis in vivo. The expression of hsa_circ_0000826 in serum was significantly increased in CRC tissues in 100-pair of CRC and according to the adjacent normal tissues by qRT-PCR assays. Moreover, the expression levels of hsa_circ_0000826 in serum of patient with liver metastasis were significantly increased than those without metastasis.
Our results suggested that hsa_circ_0000826 was induced by the hypoxia in CRC, which can be a potential biomarker of CRC liver metastasis.
hsa_circ_0000826 通过竞争性内源性 RNA 网络与 CRC 相关；然而，hsa_circ_0000826 升高的上游驱动因素尚不清楚。在这项研究中，我们旨在阐明低氧诱导的 hsa_circ_0000826 对 CRC 肿瘤发生和转移的影响。
使用 RNA scope 检测法评估 hsa_circ_0000826 在低氧条件下 CRC 细胞中的表达。通过细胞迁移和侵袭实验评估 hsa_circ_0000826 对 CRC 细胞表型的影响。裸鼠、AOM-DSS 模型鼠和 APC 鼠用于研究 circ_0000826、低氧和 CRC 之间的关系。收集 100 例 CRC 组织样本及其配对的相邻组织，通过 qRT-PCR 检测这些样本中 hsa_circ_0000826 的表达。
低氧诱导的 hsa_circ_0000826 过表达可增加 CRC 细胞在体外的恶性表型、肿瘤形成和转移能力。在 AOM-DSS 和 APC 鼠模型中，低氧条件下 CRC 组织中的 mmu_circ_0000826 水平显著升高。此外，低氧诱导的 mmu_circ_0000826 上调也可促进体内 CRC 肿瘤发生和肝转移。qRT-PCR 检测结果显示，在 100 对 CRC 组织及其相应的相邻正常组织中，血清 hsa_circ_0000826 的表达均显著升高。此外，有肝转移患者的血清 hsa_circ_0000826 表达水平明显高于无转移患者。
我们的研究结果表明，hsa_circ_0000826 是 CRC 中的低氧诱导产生的，可作为 CRC 肝转移的潜在生物标志物。
