LncRNA NORAD调控miR-136-5p/CBX4轴对急性髓系白血病细胞迁移和侵袭的影响

doi:10.3969/j.issn.1006-6233.2025.05.04

Abstract
Figure/Table
References
Related Citation (15)

Download: PDF (0 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To investigate the impacts of long non-coding RNA (LncRNA) non-coding RNA activated by DNA damage (NORAD) on migration and invasion of acute myeloid leukemia (AML) cells by adjusting microRNA-136-5p (miR-136-5p)/chromobox protein homolog 4 (CBX4) axis. Methods: Human AML cell line KG1a was used as the research subject and divided into control group, sh-NC group, sh-NORAD group, sh-NORAD+NC-inhibitor group, and sh-NORAD+miR-136-5p-inhibitor group, with six replicates in each group. The expressions of LncRNA NORAD, miR-136-5p, and CBX4 mRNA in KG1a cell lysate were detected by qRT-PCR. Plate cloning, scratch assay, and Transwell assay were performed to detect the impacts of knocking down LncRNA NORAD on proliferation, migration, and invasion of KG1a cells. Moreover, Western blot was used to detect protein expression. Results: Compared with sh-NC group and control group, the clone number, scratch healing rate, invasion number, LncRNA NORAD, CBX4 mRNA and protein, MMP-9 were decreased in sh-NORAD group, and the expression of miR-136-5p was increased (P<0.05). Compared with sh-NORAD group and sh-NORAD+NC-inhibitor group, the clone number, scratch healing rate, invasion number, CBX4 mRNA and protein and MMP-9 of sh-NORAD+miR-136-5p-inhibitor group were increased. The expression of miR-136-5p was decreased (P<0.05). LncRNA NORAD could target the negative regulation of miR-136-5p, and miR-136-5p could target the negative regulation of CBX4. Conclusion: LncRNA NORAD can regulate the miR-136-5p/CBX4 axis to promote migration and invasion of AML cells.

Key words： Acute myeloid leukemia Long non-coding RNA Non-coding RNA activated by DNA damage MicroRNA-136-5p Chromobox protein homolog 4 Migration Invasion

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors

Cite this article:

URL:

http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.05.04 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I5/723

[1] Forte D,Garcia-Fernandez M,Sanchez-Aguilera A,et al.Bone marrow mesenchymal stem cells support acute myeloid leukemia bioenergetics and enhance antioxidant defense and escape from chemotherapy[J].Cell Metab,2020,32(5):829-843.
[2] Wang S,Zhang B S,Yang Y,et al.TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137[J].Open Med (Wars),2020,16(1):95-103.
[3] Wang C H,Li Q Y,Nie L,et al.LncRNA ANRIL promotes cell proliferation,migration and invasion during acute myeloid leukemia pathogenesis via negatively regulating miR-34a[J].Int Biochem Cell Biol,2020,119(1):105666.
[4] Xie K Y,Chen S Z,Wang Y,et al.Establishment and validation of a prognostic immune-related lncRNA risk model for acute myeloid leukemia[J].Transl Cancer Res,2023,12(12):3693-3702.
[5] Masoud Eslami M,Soufizomorrod M,Ahmadvand M.High expression of long noncoding RNA NORAD is associated with poor clinical outcomes in non-M3 acute myeloid leukemia patients[J].Hematol Oncol Stem Cell Ther,2021,1(21):1-10.
[6] Zhang R,Huo C H.Long noncoding RNA SOCS2-AS promotes leukemogenesis in FLT3-ITD+ acute myeloid leukemia through miRNA-221[J].Onco Targets Ther,2020,13(1):2925-2934.
[7] Liu C,Zhong L,Shen C,et al.CRNDE enhances the expression of MCM5 and proliferation in acute myeloid leukemia KG-1a cells by sponging miR-136-5p[J].Sci Rep,2021,11(1):16755-16765.
[8] de Groot A P,de Haan G.How CBX proteins regulate normal and leukemic blood cells[J].FEBS Lett,2024,598(22):2788-2806.
[9] Lv C,Wang J,Dai S,et al.Long non-coding RNA NORAD induces phenotypic regulation of vascular smooth muscle cells through regulating microRNA-136-5p-targeted KDM1A[J].Cell Cycle,2021,20(20):2137-2148.
[10] Zhao J,Yang T,Li L.LncRNA FOXP4-AS1 is involved in cervical cancer progression via regulating miR-136-5p/CBX4 axis[J].Onco Targets Ther,2020,13(1):2347-2355.
[11] Chang F,Wang L,Kim Y,et al.The aryl Hydrocarbon receptor regulates invasiveness and motility in acute myeloid leukemia cells through expressional regulation of non-muscle myosin heavy chain IIA[J].Int Mol Sci,2024,25(15):8147-8161.
[12] Xu D,Jiang J,He G,et al.KMT2A is targeted by miR-361-3p and modulates leukemia cell's abilities to proliferate,migrate and invade[J].Hematology,2023,28(1):2225341-225351.
[13] Mishra S,Liu J,Chai L,et al.Diverse functions of long noncoding RNAs in acute myeloid leukemia:emerging roles in pathophysiology,prognosis,and treatment resistance[J].Curr Opin Hematol,2022,29(1):34-43.
[14] Tian Q,Yan X,Yang L,et al.LncRNA NORAD promotes hepatocellular carcinoma progression via regulating miR-144-3p/SEPT2[J].Am Transl Res,2020,12(5):2257-2266.
[15] Wang K,Chen Z,Qiao X,et al.LncRNA NORAD regulates the mechanism of the miR-532-3p/Nectin-4 axis in pancreatic cancer cell proliferation and angiogenesis[J].Toxicol Res (Camb),2023,12(3):425-432.
[16] Wang Y,Wang F,Lu Y,et al.MiR-140 targets lncRNA FAM230B to suppress cell proliferation in acute myeloid leukemia running title:MiR-140 targets FAM230B in AML[J].Hematology,2022,27(1):700-705.
[17] Yang B,Zang J,Yuan W,et al.The miR-136-5p/ROCK1 axis suppresses invasion and migration,and enhances cisplatin sensitivity in head and neck cancer cells[J].Exp Ther Med,2021,21(4):317.
[18] Chen Y H,Zhang X,Ko K Y,et al.CBX4 regulates replicative senescence of WI-38 fibroblasts[J].Oxid Med Cell Longev,2022:5503575.
[19] Li W,Chen H,Wang Z,et al.Chromobox 4 (CBX4) promotes tumor progression and stemness via activating CDC20 in gastric cancer[J].Gastrointest Oncol,2022,13(3):1058-1072.
[20] Li S,Zhao Y,Chen X.Microarray expression profile analysis of circular RNAs and their potential regulatory role in bladder carcinoma[J].Oncol Rep,2021,45(1):239-253.