MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

Liu, Liru; Ren, Weihua; Chen, Kuisheng

doi:10.1159/000475277

Cited by 89 publications

(61 citation statements)

References 39 publications

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“…The suppression of miR‐34a expression was related to poor clinical outcome and impaired treatment efficacy in patients suffering from AML, indicating that miR‐34a concentration in LSCs may be an innovative predictor of AML clinical outcome. This observation is in line with the results of the study by Liu et al, wherein miR‐34a suppression was inhibited in AML cells …”

Section: Discussionsupporting

confidence: 92%

MicroRNA‐34a‐mediated death of acute myeloid leukemia stem cells through apoptosis induction and exosome shedding inhibition via histone deacetylase 2 targeting

et al. 2020

IUBMB Life

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We investigated the role of leukemia stem cells in chemoresistance and recurrence of acute myeloid leukemia. Total RNA was isolated from cells or tissues using TRIzol reagent. Cell viability was assessed with the tetrazolium assay. MicroRNA‐34a (miR‐34a), which acts on cell death regulation pathways, was noticeably downregulated in non‐M3 acute myeloid leukemia stem cells compared with normal hematopoietic stem cells. Furthermore, inhibition of miR‐34a‐mediated suppression in leukemia stem cells was associated with poor clinical outcomes and impaired treatment efficacy in acute myeloid leukemia. Transfection with a miR‐34a mimic triggered leukemia stem cell death and prevented leukemia. Bioinformatics analysis and a dual‐luciferase reporter assay showed that miR‐34a targeted the 3′‐untranslated region of histone deacetylase 2, and the reinforced expression of miR‐34a remarkably stimulated the expression of histone deacetylase 2 in leukemia stem cells. Ectopic miR‐34a expression triggered death of leukemia stem cells via pathways involving the Janus kinase 1‐signal transducer and activator of transcription 2‐p53 axis. Targeting leukemia stem cells to trigger cell death through upregulation of miR‐34a expression could be used to diagnose and treat acute myeloid leukemia.

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Section: Discussionsupporting

confidence: 92%

MicroRNA‐34a‐mediated death of acute myeloid leukemia stem cells through apoptosis induction and exosome shedding inhibition via histone deacetylase 2 targeting

et al. 2020

IUBMB Life

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“…HMGB1 could activate autophagy to protect cancer cell from the chemotherapy‐induced apoptosis in leukemia . miR‐34a was reported to target HMGB1 and inhibited the autophagy in acute myeloid leukemia cells . However, the mechanism of miR‐34a/HMGB1 axis in colon cancer remains unknown and needs to be further explored.…”

Section: Introductionmentioning

confidence: 99%

LncRNA NEAT1 knockdown attenuates autophagy to elevate 5‐FU sensitivity in colorectal cancer via targeting miR‐34a

Liu

Zhang

et al. 2019

Cancer Medicine

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Backgrounds: Colorectal carcinoma (CRC) is a common malignant tumor.Increasing evidences indicated that CRC showed a resistance to 5-fluorouracil (5-FU) and further resulted in a poor prognosis. In this study, we aim to investigate the effect of long noncoding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) on cell viability, sensitivity to 5-FU, and autophagy of CRC cell lines. Methods: MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide) was used to detect cell viability, immunofluorescent staining was used to detect autophagy puncta, and luciferase reporter system was used to determine binding ability between miR-34a and NEAT1 or putative targets. Additionally, indicated mRNAs and protein expressions were determined by qRT-PCR or western blotting, respectively. Results: We found that NEAT1 expression was increased in CRC tissues and cells, which showed a negative correlation with miR-34a expression. In addition, NEAT1 knockdown noticeably inhibited the proliferation of CRC cells and enhanced 5-FU sensitivity. It revealed that NEAT1 knockdown suppressed the LC3 puncta and the expressions of Beclin-1, ULK1, and ratio of LC3II/I. Overexpression of miR-34a showed similar trends with NEAT1 knockdown. miR-34a was validated to target the putative binding sites in 3′-UTR of HMGB1, ATG9A, and ATG4B, which are involved in the activation of autophagy. Inhibition of miR-34a or overexpression of HMGB1 could effectively reverse elevated 5-FU sensitivity upon NEAT1 knockdown. In addition, 3-MA reversed NEAT1 overexpression-induced resistance in HT29 cells. Conclusion: These findings indicate that LncRNA NEAT1 could target miR-34a and promote autophagy to facilitate 5-FU chemoresistance in CRC. K E Y W O R D Sautophagy, colorectal carcinoma, HMGB1, LncRNA NEAT1, miR-34a

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“…Previous studies have measured the expression of miR-34a in several hematologic diseases, including multiple myeloma (30), primary myelofibrosis (20), and acute myelocytic leukemia (31). These findings revealed the role of miR-34a in lineage choice and fate decision in hematopoiesis.…”

Section: Discussionmentioning

confidence: 88%

MicroRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells

Zeng

et al. 2019

FASEB j.

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Hematopoietic stem cells (HSCs) establish the entire hematopoietic system and maintain lifelong hematopoiesis. Previous studies have reported the significance of microRNAs (miRNAs) in the regulation of self‐renewal and differentiation of HSCs. In this study, we show that the expression of miRNA 34a (miR‐34a) is markedly up‐regulated in HSCs from mice subjected to ionizing radiation (IR). Reduced numbers and DNA damage repair, as well as increased apoptosis, are observed in HSCs from miR‐34a–deficient mice induced by irradiation, although miR‐34a is dispensable for steady‐state hematopoiesis. Further investigations show that HSCs deficient in miR‐34a exhibit decreased expressions of DNA repair–associated genes involved in homologous recombination and nonhomologous end joining. Competitive transplantation confirms that loss of miR‐34a leads to more severe impairment of the long‐term hematopoietic function of HSCs after irradiation exposure. Consistently, treating mice with an miR‐34a agomir can significantly alleviate irradiation‐induced DNA damage in HSCs. Our findings demonstrate that miR‐34a contributes to promoting HSCs' survival after irradiation, which provides a promising approach for protecting HSCs from IR.—Zeng, H., Hu, M., Lu, Y., Zhang, Z., Xu, Y., Wang, S., Chen, M., Shen, M., Wang, C., Chen, F., Du, C., Tang, Y., Su, Y., Chen, S., Wang, J. MicroRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells. FASEB J. 33, 8138–8147 (2019). http://www.fasebj.org

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MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

Cited by 89 publications

References 39 publications

MicroRNA‐34a‐mediated death of acute myeloid leukemia stem cells through apoptosis induction and exosome shedding inhibition via histone deacetylase 2 targeting

MicroRNA‐34a‐mediated death of acute myeloid leukemia stem cells through apoptosis induction and exosome shedding inhibition via histone deacetylase 2 targeting

LncRNA NEAT1 knockdown attenuates autophagy to elevate 5‐FU sensitivity in colorectal cancer via targeting miR‐34a

MicroRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells

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