LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia

被引:6
作者
Zhai, Hong [1 ]
Zhao, Junting [1 ]
Pu, Juan [1 ]
Zhao, Pan [1 ]
Wei, Jin [1 ]
机构
[1] North Sichuan Med Coll, Affiliated Hosp, Dept Hematol, Nanchong, Peoples R China
关键词
Acute myeloid leukemia; LncRNA-DUXAP8; Apoptosis; Glycolysis; Wnt/beta-catenin signaling pathway; LONG NONCODING RNA; METABOLIC-DISORDERS; SELF-RENEWAL; EXPRESSION; CLASSIFICATION; LNCRNA; DUXAP8; CELLS;
D O I
10.4274/tjh.galenos.2021.2020.0769
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, accounting for approximately 70% of acute leukemias. Long noncoding RNA-DUXAP8 (IncRNA-DUXAP8) has been found to be abnormally expressed in a variety of tumors. However, its function and mechanism in AML have not been studied. We investigate the effect of IncRNA-DUXAP8 on AML and its mechanism so as to provide a new theoretical basis for the diagnosis and treatment of AML. Materials and Methods: The expression of lncRNA-DUXAP8 in AML bone marrow tissues and the THP-1, HL-60, TF-1, AML193, and U937 cell lines was detected by qRT-PCR. It was then altered by transfecting plasmids overexpressing si-DUXAP8 and lncRNA-DUXAP8, respectively. CCK8 and cell colony assay were performed to evaluate the proliferation ability of AML cells. In addition, flow cytometry was used to observe the apoptosis process. Glucose and lactate kits were utilized to detect glucose consumption and lactate levels. Finally, western blotting was performed to detect the expression of proteins related to the Wnt/beta-catenin signaling pathway in cells. Results: LncRNA-DUXAP8 was downregulated in both AML bone marrow tissues and cell lines. Upon interfering with lncRNA-DUXAP8 in AML cell line THP-1, AML cell proliferation and glycolysis were promoted while cell apoptosis was inhibited. The opposite results were obtained after overexpressing lncRNA-DUXAP8. Meanwhile, western blotting confirmed that interference with lncRNA-DUXAP8 stimulated the expression of proteins Wnt5a, H-catenin, c-Myc, and cyclin-D1 in the Wnt/beta-catenin pathway. Moreover, overexpression of lncRNA-DUXAP8 inhibited the expression of Wnt/beta-catenin pathway proteins. Finally, LiCl, an activator of the Wnt/beta-catenin pathway, reversed the regulation of AML cells by lncRNA-DUXAP8 upregulation compared with the DUXAP group. Conclusion: This study showed that lncRNA-DUXAP8 regulated the Wnt/beta-catenin signaling pathway to inhibit glycolysis and induce apoptosis in AML This experiment has provided new angles and an experimental basis for treating patients with AML.
引用
收藏
页码:264 / 272
页数:9
相关论文
共 39 条
[1]  
Almeida Antonio M, 2016, Leuk Res Rep, V6, P1, DOI 10.1016/j.lrr.2016.06.001
[2]   The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia [J].
Arber, Daniel A. ;
Orazi, Attilio ;
Hasserjian, Robert ;
Thiele, Jurgen ;
Borowitz, Michael J. ;
Le Beau, Michelle M. ;
Bloomfield, Clara D. ;
Cazzola, Mario ;
Vardiman, James W. .
BLOOD, 2016, 127 (20) :2391-2405
[3]   New aspects of the Warburg effect in cancer cell biology [J].
Bensinger, Steven J. ;
Christofk, Heather R. .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2012, 23 (04) :352-361
[4]   Chibby suppresses aerobic glycolysis and proliferation of nasopharyngeal carcinoma via the Wnt/β-catenin-Lin28/let7-PDK1 cascade [J].
Cai, Cheng-fu ;
Ye, Guo-dong ;
Shen, Dong-yan ;
Zhang, Wei ;
Chen, Mao-li ;
Chen, Xin-xin ;
Han, Da-xiong ;
Mi, Yan-jun ;
Luo, Qi-cong ;
Cai, Wang-yu ;
Yang, Shu-yu .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2018, 37
[5]   Linking Long Noncoding RNA Localization and Function [J].
Chen, Ling-Ling .
TRENDS IN BIOCHEMICAL SCIENCES, 2016, 41 (09) :761-772
[6]   YAP triggers the Wnt/β-catenin signalling pathway and promotes enterocyte self-renewal, regeneration and tumorigenesis after DSS-induced injury [J].
Deng, Feihong ;
Peng, Liang ;
Li, Zhijun ;
Tan, Gao ;
Liang, Erbo ;
Chen, Shengbo ;
Zhao, Xinmei ;
Zhi, Fachao .
CELL DEATH & DISEASE, 2018, 9
[7]   Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia [J].
DiNardo, C. D. ;
Jonas, B. A. ;
Pullarkat, V. ;
Thirman, M. J. ;
Garcia, J. S. ;
Wei, A. H. ;
Konopleva, M. ;
Doehner, H. ;
Letai, A. ;
Fenaux, P. ;
Koller, E. ;
Havelange, V. ;
Leber, B. ;
Esteve, J. ;
Wang, J. ;
Pejsa, V. ;
Hajek, R. ;
Porkka, K. ;
Illes, A. ;
Lavie, D. ;
Lemoli, R. M. ;
Yamamoto, K. ;
Yoon, S. -S. ;
Jang, J. -H. ;
Yeh, S. -P. ;
Turgut, M. ;
Hong, W. -J. ;
Zhou, Y. ;
Potluri, J. ;
Pratz, K. W. .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (07) :617-629
[8]   Acute Myeloid Leukemia [J].
Doehner, Hartmut ;
Weisdorf, Daniel J. ;
Bloomfield, Clara D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (12) :1136-1152
[9]   PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element [J].
Ebralidze, Alexander K. ;
Guibal, Florence C. ;
Steidl, Ulrich ;
Zhang, Pu ;
Lee, Sanghoon ;
Bartholdy, Boris ;
Jorda, Meritxell Alberich ;
Petkova, Victoria ;
Rosenbauer, Frank ;
Huang, Gang ;
Dayaram, Tajhal ;
Klupp, Johanna ;
O'Brien, Karen B. ;
Will, Britta ;
Hoogenkamp, Maarten ;
Borden, Katherine L. B. ;
Bonifer, Constanze ;
Tenen, Daniel G. .
GENES & DEVELOPMENT, 2008, 22 (15) :2085-2092
[10]   Autophagy promotes metastasis and glycolysis by upregulating MCT1 expression and Wnt/β-catenin signaling pathway activation in hepatocellular carcinoma cells [J].
Fan, Qing ;
Yang, Liang ;
Zhang, Xiaodong ;
Ma, Yingbo ;
Li, Yan ;
Dong, Lei ;
Zong, Zhihong ;
Hua, Xiangdong ;
Su, Dongming ;
Li, Hangyu ;
Liu, Jingang .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2018, 37