LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia Via the MiR-378g/ERBB2 Axis

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2022 Oct 17

PMID 36248434

Authors

Xiaolu Song

Yirui Chen

Ye Peng

Xiaogang Wang

Sujie Zheng

Fangfang Shi

Jianping Lan

Affiliations

Soon will be listed here.

Abstract

Objective: Considering the role of lncRNAs reported as regulators in acute myeloid leukemia (AML) progression, the current research aims to investigate the role of PAX8-AS1 in chemo-resistant AML.

Methods: Human AML cells HL60 and human doxorubicin (ADM)-resistant AML cells (HL60/ADM cells) were used to establish models of chemo-sensitive AML and refractory/recurrent AML, respectively. CCK-8 assay and flow cytometry were used to determine cell resistance to ADM, viability, and apoptosis. PAX8-AS1, miR-378g, and ERBB2 expressions in the models and/or AML patients were quantified via qRT-PCR or Western blot. The miRNA/mRNA axis targeted by PAX8-AS1 was analyzed using Starbase, TargetScan, or GEO and validated through a dual-luciferase reporter assay. The expressions of Bcl-2, Bax, and C Caspase-3 in cells were quantitated by Western blot.

Results: The highly expressed PAX8-AS1 was observed in AML patients and HL60 cells, which was more evident in refractory/recurrent AML patients and HL60/ADM cells. Compared with that in ADM-treated parental HL60 cells, the viability of ADM-treated HL60/ADM cells remained strong. PAX8-AS1 overexpression increased viability and Bcl-2 expression, while diminishing apoptosis, Bax, and C Caspase-3 expressions in HL60 cells. However, the abovementioned aspects were oppositely impacted by PAX8-AS1 silencing in HL60/ADM cells. PAX8-AS1 directly targeted miR-378g, whose expression pattern is opposite to that of PAX8-AS1 in AML. MiR-378g upregulation abrogated the effects of PAX8-AS1 overexpression on HL60 cells. MiR-378g downregulation offset PAX8-AS1 silencing-induced effects on HL60/ADM cells. Moreover, ERBB2 was recognized as the target of miR-378g, with a higher expression in HL60/ADM cells than in HL60 cells.

Conclusion: PAX8-AS1 silencing decreases cell viability, enhances apoptosis, and suppresses ADM resistance in AML via regulating the miR-378g/ERBB2 axis.

Citing Articles

Retracted: LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia via the miR-378g/ERBB2 Axis.

And Alternative Medicine E Evid Based Complement Alternat Med. 2023; 2023:9829428.

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Dai R, Yang X, He W, Su Q, Deng X, Li J Korean Circ J. 2023; 53(3):151-167.

PMID: 36914604 PMC: 10011218. DOI: 10.4070/kcj.2022.0242.

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