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Hsa_circ_0001806作为一种竞争性内源RNA，通过上调COL1A1促进结肠癌细胞的干性。

Hsa_circ_0001806 Acts as a ceRNA to Facilitate the Stemness of Colorectal Cancer Cells by Increasing COL1A1.

作者信息

Sun Jie, Liu Jie, Zhu Qilin, Xu Feng, Kang Liumin, Shi Xiaohua

机构信息

Department of Gastroenterology, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu 215153, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jun 30;13:6315-6327. doi: 10.2147/OTT.S255485. eCollection 2020.

DOI:10.2147/OTT.S255485
PMID:32636650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7335295/
Abstract

BACKGROUND

The aberrant expression of circular RNAs (circRNAs) has been identified as a novel trait of cancers. However, the role of circRNAs in colorectal cancer (CRC) remains to be elucidated.

METHODS

Informatic analysis was performed to identify circRNAs in CRC tissues and adjacent tissues. Gain- and loss-of-function experiments were constructed to analyze hsa_circ_001806 roles in CRC cell stemness by sphere-formation, ALDH activity, stemness marker expression and tumor-initiating ability assays. CCK8 cell viability was carried out to evaluate hsa_circ_0001806 roles in CRC cell viability. Luciferase reporter and pull-down assays were used to reveal the underlying mechanisms.

RESULTS

Hsa_circ_0001806 was significantly upregulated in CRC tissues and correlated with TNM stage, depth of invasion, lymphatic metastasis and distant metastasis. Hsa_circ_0001806 promoted the stemness of CRC cells, as evident by increasing sphere-formation ability, ALDH1 activity and stemness marker expression while had no effect on cell viability. Mechanistically, the same miR-193-5p-binding sites are shared between hsa_circ_0001806 and COL1A1. Hsa_circ_0001806 upregulates COL1A1 expression in a miR-193-5p-dependent manner, which is essential for hsa_circ_0001806-mediated regulation on CRC cell stemness.

CONCLUSION

CircRNA hsa_circ_0001806 may act as a promising therapeutic target by facilitating the stemness of CRC cells via activating the hsa_circ_0001806/miR-193a-5p/COL1A1 axis.

摘要

背景

环状RNA（circRNAs）的异常表达已被确定为癌症的一种新特征。然而，circRNAs在结直肠癌（CRC）中的作用仍有待阐明。

方法

进行信息分析以鉴定CRC组织和相邻组织中的circRNAs。构建功能获得和功能丧失实验，通过成球实验、醛脱氢酶（ALDH）活性、干性标志物表达和肿瘤起始能力测定来分析hsa_circ_001806在CRC细胞干性中的作用。采用CCK8细胞活力实验评估hsa_circ_0001806在CRC细胞活力中的作用。使用荧光素酶报告基因和下拉实验揭示潜在机制。

结果

hsa_circ_0001806在CRC组织中显著上调，且与TNM分期、浸润深度、淋巴转移和远处转移相关。hsa_circ_0001806促进CRC细胞的干性，表现为成球能力、ALDH1活性和干性标志物表达增加，而对细胞活力无影响。机制上，hsa_circ_0001806和COL1A1共享相同的miR-193-5p结合位点。hsa_circ_0001806以miR-193-5p依赖的方式上调COL1A1表达，这对于hsa_circ_0001806介导的CRC细胞干性调节至关重要。

结论

环状RNA hsa_circ_0001806可能通过激活hsa_circ_0001806/miR-193a-5p/COL1A1轴促进CRC细胞的干性，从而成为一个有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/347426e2fcb3/OTT-13-6315-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/f950e69f5846/OTT-13-6315-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/cc2a9f456636/OTT-13-6315-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/014a9218638d/OTT-13-6315-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/5d163154fd8d/OTT-13-6315-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/129fc0f9353c/OTT-13-6315-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/f5da20494916/OTT-13-6315-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/347426e2fcb3/OTT-13-6315-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/f950e69f5846/OTT-13-6315-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/cc2a9f456636/OTT-13-6315-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/014a9218638d/OTT-13-6315-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/5d163154fd8d/OTT-13-6315-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/129fc0f9353c/OTT-13-6315-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/f5da20494916/OTT-13-6315-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef9/7335295/347426e2fcb3/OTT-13-6315-g0007.jpg

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