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一种新型环状 RNA,hsa_circ_0030998 通过海绵吸附 miR-558 抑制肺癌肿瘤发生和紫杉醇耐药性。

A novel circular RNA, hsa_circ_0030998 suppresses lung cancer tumorigenesis and Taxol resistance by sponging miR-558.

机构信息

Department of Thoracic Surgery, Tianjin First Central Hospital, China.

Department of Oncology Armed Police Characteristic Medical Center, Tianjin, China.

出版信息

Mol Oncol. 2021 Aug;15(8):2235-2248. doi: 10.1002/1878-0261.12852. Epub 2021 Feb 10.

DOI:10.1002/1878-0261.12852
PMID:33190405
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8333779/
Abstract

Circular RNAs (circRNAs) are single-stranded RNAs which form a covalently closed continuous loop. Although originally shown to be non-protein-coding, some circRNAs can give rise to micropeptides. circRNAs have also been shown to play essential regulatory roles in a variety of developmental and disease processes. In a previous study, hsa_circ_0030998 was identified as a circRNA downregulated in lung cancer, but its potential implications and mechanisms in lung cancer were not addressed. Here, we showed that overexpressing circ_0030998 decreased proliferation, migration, and invasion of lung cancer cells, while also dampening resistance to Taxol, a classical antitumor drug. Depleting circ_0030998 reversed these phenotypic effects. A high circ_0030998 expression was correlated with a high survival rate in lung cancer patients. Additionally, we found circ_0030998 could downregulate miR-558 expression, serving as a microRNA sponge. In conclusion, our data support that hsa_circ_0030998 can slow down the progression of lung cancer by targeting miR-558 and suppress malignant phenotypes such as proliferation, migration, and invasion progression of lung cancer cells. Therefore, we highlight that circ_0030998 could be a novel tumor suppressor of lung cancer.

摘要

环形 RNA(circRNAs)是一种单链 RNA,形成共价闭合的连续环。尽管最初被证明是非编码蛋白的,但一些 circRNAs 可以产生微小肽。circRNAs 还被证明在多种发育和疾病过程中发挥着重要的调节作用。在之前的一项研究中,hsa_circ_0030998 被鉴定为肺癌中下调的 circRNA,但它在肺癌中的潜在意义和机制尚未得到解决。在这里,我们表明过表达 circ_0030998 可降低肺癌细胞的增殖、迁移和侵袭能力,同时还降低了对 Taxol(一种经典的抗肿瘤药物)的耐药性。circ_0030998 的缺失逆转了这些表型效应。circ_0030998 的高表达与肺癌患者的高生存率相关。此外,我们发现 circ_0030998 可以下调 miR-558 的表达,作为 microRNA 海绵。总之,我们的数据支持 hsa_circ_0030998 通过靶向 miR-558 减缓肺癌的进展,并抑制肺癌细胞增殖、迁移和侵袭等恶性表型。因此,我们强调 circ_0030998 可能是肺癌的一种新型肿瘤抑制因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/ae71028926f9/MOL2-15-2235-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/574ad8e7c249/MOL2-15-2235-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/30d78454b791/MOL2-15-2235-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/a8767c7e1b72/MOL2-15-2235-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/d6c92d355cee/MOL2-15-2235-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/edd7d889e0a7/MOL2-15-2235-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/1b365df5f936/MOL2-15-2235-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/ae71028926f9/MOL2-15-2235-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/574ad8e7c249/MOL2-15-2235-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/30d78454b791/MOL2-15-2235-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/a8767c7e1b72/MOL2-15-2235-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/d6c92d355cee/MOL2-15-2235-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/edd7d889e0a7/MOL2-15-2235-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/1b365df5f936/MOL2-15-2235-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4257/8333779/ae71028926f9/MOL2-15-2235-g008.jpg

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