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

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

doi:10.1016/j.omtn.2020.01.021

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

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

Authors

Juhua Yang¹, Zhao Yin², Yumin Li³, Yanjun Liu¹, Guiping Huang¹, Chunming Gu², Jia Fei⁴

Affiliations

¹ 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.
² 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.
³ Medical Laboratory of Shenzhen Luohu People's Hospital, Shenzhen, China.
⁴ 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. Electronic address: tfeijia@jnu.edu.cn.

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.

Keywords: CML; H19; RNA pull-down assays; antisense; bioinformatics prediction; long non-coding RNA; mass spectrometry; target identification; transcription in vitro.