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长链非编码RNA H19靶点的鉴定及其在慢性髓性白血病中的作用

The Identification of Long Non-coding RNA H19 Target and Its Function in Chronic Myeloid Leukemia.

作者信息

Yang Juhua, Yin Zhao, Li Yumin, Liu Yanjun, Huang Guiping, Gu Chunming, Fei Jia

机构信息

Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China; Engineering Technology Research Center of Drug Development for Small Nucleic Acid, Guangdong Province, China; Antisense Biopharmaceutical Technology Co., Ltd., Guangzhou, China.

Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China; Engineering Technology Research Center of Drug Development for Small Nucleic Acid, Guangdong Province, China; Antisense Biopharmaceutical Technology Co., Ltd., Guangzhou, China; Insititute of Chinese Integrative Medicine, Medical College of Jinan University, Guangzhou 510632, China.

出版信息

Mol Ther Nucleic Acids. 2020 Mar 6;19:1368-1378. doi: 10.1016/j.omtn.2020.01.021. Epub 2020 Jan 25.

Abstract

H19 is a long non-coding RNA which was lowly expressed in chronic myeloid leukemia (CML). Here, we found that the overexpression of H19 significantly inhibited cell viability and colony formation and prolongs survival in CML cell lines and three xenografted mouse models. The H19 target proteins and microRNAs (miRNAs) were identified using a combination of computational prediction and RNA pull-down, including PCBP1, FUS protein, and miR-19a-3p and miR-106b-5p. Targeting PCBP1, FUS protein, miR-19a-3p, and miR-106b-5p significantly inhibits the cell growth and colony formation of CML cell lines. Co-overexpression of H19 and PCBP1, FUS, miR-19a-3p, and miR-106b-5p decreases the inhibitory effect of H19 in CML. These findings might provide a novel molecular insight into CML.

摘要

H19是一种长链非编码RNA,在慢性髓性白血病(CML)中低表达。在此,我们发现H19的过表达显著抑制CML细胞系和三种异种移植小鼠模型中的细胞活力和集落形成,并延长生存期。通过计算预测和RNA下拉相结合的方法鉴定了H19的靶蛋白和微小RNA(miRNA),包括PCBP1、FUS蛋白以及miR-19a-3p和miR-106b-5p。靶向PCBP1、FUS蛋白、miR-19a-3p和miR-106b-5p可显著抑制CML细胞系的细胞生长和集落形成。H19与PCBP1、FUS、miR-19a-3p和miR-106b-5p的共过表达降低了H19对CML的抑制作用。这些发现可能为CML提供新的分子见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5133/7044501/828f562d681b/gr1.jpg

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