The circular RNA 001971/miR-29c-3p axis modulates colorectal cancer growth, metastasis, and angiogenesis through VEGFA (Retracted article. See vol. 41, 2022)
The circular RNA 001971/miR-29c-3p axis modulates colorectal cancer growth, metastasis, and angiogenesis through VEGFA (Retracted article. See vol. 41, 2022)
复制标题
DOI：
10.1186/s13046-020-01594-y
复制
发表时间：
2020-05-19
影响因子：
11.3
通讯作者：
Zhang, Mu
中科院分区：
文献类型：
--
作者：
Chen, Chen;Huang, Zhiguo;Zhang, Mu
结直肠癌（Colorectal cancer，CRC）是世界上最常见的恶性肿瘤之一。血管生成是维持肿瘤细胞存活和侵袭性的关键事件。血管内皮生长因子A（VEGFA）是肿瘤细胞分泌的最重要的促血管生成因子之一，其表达在CRC中频繁上调。方法采用MTT法检测大肠癌细胞的存活率。采用Transwell法检测靶细胞的侵袭能力。通过免疫印迹法测定相对蛋白水平。HE染色和免疫组化染色观察组织病理学特征。进行RIP测定以验证预测的基因之间的结合。结果我们观察到circ-001971在CRC组织样品和细胞中的表达显著增加。Circ-001971敲低抑制CRC细胞增殖和侵袭的能力以及体外HUVEC管形成，以及体内携带SW 620细胞衍生肿瘤的小鼠中的肿瘤生长。在肿瘤组织样品中，circ-001971和VEGFA的表达显著增加，而miR-29 c-3 p的表达降低。Circ-001971通过充当ceRNA减轻miR-29 c-3 p诱导的VEGFA抑制，从而加重CRC的增殖、侵袭和血管生成。与上述发现一致，在肿瘤组织样品中VEGFA的表达增加，而miR-29 c-3 p的表达降低。miR-29 c-3 p与circ-001971和VEGFA均呈负相关，而circ-001971与VEGFA呈正相关。结论circ-001971/miR-29 c-3 p轴通过靶向VEGFA调控CRC细胞增殖、侵袭和血管生成。
Background Colorectal cancer (CRC) is one of the most common malignant tumors globally. Angiogenesis is a key event maintaining tumor cell survival and aggressiveness. The expression of vascular endothelial growth factor A (VEGFA), one of the most significant tumor cell-secreted proangiogenic factors, is frequently upregulated in CRC. Methods The MTT assay was used to detect the viability of CRC cells. Transwell assays were performed to detect the invasion capacity of target cells. Relative protein levels were determined by immunoblotting. Pathological characteristics of tissues were detected by H&E staining and immunohistochemical (IHC) staining. A RIP assay was conducted to validate the predicted binding between genes. Results We observed that circ-001971 expression was dramatically increased in CRC tissue samples and cells. Circ-001971 knockdown suppressed the capacity of CRC cells to proliferate and invade and HUVEC tube formation in vitro, as well as tumor growth in mice bearing SW620 cell-derived tumors in vivo. The expression of circ-001971 and VEGFA was dramatically increased whereas the expression of miR-29c-3p was reduced in tumor tissue samples. Circ-001971 relieved miR-29c-3p-induced inhibition of VEGFA by acting as a ceRNA, thereby aggravating the proliferation, invasion and angiogenesis of CRC. Consistent with the above findings, the expression of VEGFA was increased, whereas the expression of miR-29c-3p was decreased in tumor tissue samples. miR-29c-3p had a negative correlation with both circ-001971 and VEGFA, while circ-001971 was positively correlated with VEGFA. Conclusions In conclusion, the circ-001971/miR-29c-3p axis modulated CRC cell proliferation, invasion, and angiogenesis by targeting VEGFA.