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Cancer Lett. 2019 Jul 10;454:26-36. doi: 10.1016/j.canlet.2019.03.055. Epub 2019 Apr 5.

H22954, a novel long non-coding RNA down-regulated in AML, inhibits cancer growth in a BCL-2-dependent mechanism.

Author information

1
Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou, 215000, China; Departments of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Departments of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. Electronic address: qixf-sz@hotmail.com.
2
State Key Laboratory of Radiation Medicine and Protection, Soochow University School of Medicine, Suzhou, 215123, China; Collaborative Innovation Center of Radiological Medicine, Soochow University School of Medicine, Suzhou, 215123, China.
3
Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.
4
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200438, China.
5
Departments of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. Electronic address: szchenzx@263.net.
6
Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou, 215000, China. Electronic address: wuqy@suda.edu.cn.

Abstract

Long non-coding RNAs (lncRNAs) are important in cancer biology. In this study, we analyzed differentially expressed genes in CD34 + hematopoietic cells and identified a novel lncRNA, H22954, which was down-regulated in acute myeloid leukemia (AML) patients. In cultured AML cells and mouse xenograft models, H22954 expression inhibited cell proliferation and tumor growth, respectively. Bioinformatic analysis and RNA antisense purification assay indicated that H22954 targeted the 3' untranslated region of the BCL2 gene. In luciferase assays, H22954 expression inhibited BCL2 expression. In transfected K562 cells and mouse xenograft tumors, H22954 overexpression reduced BCL-2 protein levels and promoted cell death. In AML patients, H22954 expression inversely correlated with BCL-2 protein levels in bone marrow cells, blast cell numbers and disease prognosis. These results indicate that H22954 is a novel regulator of BCL-2 and that reduced H22954 expression may play an important role in the pathogenesis of AML.

KEYWORDS:

AML; Apoptosis; BCL-2; H22954; Long non-coding RNA

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