miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis

Bai, Hao; Cao, Zhongwei; Deng, Chao; Zhou, Lili; Wang, Chun

doi:10.1007/s00432-011-1137-3

Cited by 52 publications

(43 citation statements)

References 26 publications

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“…Likewise, MIR181A was able to affect ATG5 levels and autophagy in K562 agents Ara-C, vincristine and cisplatin in glioma, leukemia, gastric cancer or lung cancer cell lines. 33,34,58,59 Similarly, we could observe that MIR181A overexpression potentiated the toxicity of the cancer therapy agent cisplatin in MCF-7 breast cancer cells (Fig. S10).…”

Section: Discussionmentioning

confidence: 69%

“…BCL2, an antiapoptotic member of the BCL2 family that was involved in autophagy regulation through sequestration of the autophagy protein BECN1, is among the known targets of MIR181A. [31][32][33][34] In our system, overexpression of the miRNA did not significantly affect the levels of BCL2 protein under nonstarved or starved conditions in MCF-7 cells (Fig. S6A), whereas, in line with other starvation was more prominent after Ant-181a transfection compared with controls (Fig.…”

Section: Mir181a Blocked Starvation-induced Autophagy In Mcf-7mentioning

confidence: 84%

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MIR181Aregulates starvation- and rapamycin-induced autophagy through targeting ofATG5

et al. 2013

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Section: Discussionmentioning

confidence: 69%

Section: Mir181a Blocked Starvation-induced Autophagy In Mcf-7mentioning

confidence: 84%

MIR181Aregulates starvation- and rapamycin-induced autophagy through targeting ofATG5

et al. 2013

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“…28 Recently, it was shown that ectopic expression of miR-181a sensitizes AML cell lines to chemotherapy. 29 In addition, we reported that higher miR-181a expression was associated with the presence of CEBPA mutations in CN-AML patients. 5 In this study, we show that higher miR-181a expression in CN-AML patients is predominantly present in the patients harboring CEBPA N-terminal mutations, as opposed to those having single C-terminal mutations or wild-type CEBPA.…”

mentioning

confidence: 96%

“…43,44 Recently, it was demonstrated that miR-181a can sensitize a chemotherapyresistant HL60 cell line to Ara-C treatment. 29 Having found that miR-181a is up-regulated in response to lenalidomide, we asked whether pretreatment of AML cells with this compound can similarly sensitize the cells to Ara-C.When THP-1 cells were treated with either 3M lenalidomide, 1M Ara-C, or both compounds simultaneously, an additive cytotoxic effect was observed ( Figure 6A). Using THP-1 cells transiently transfected with antagomiR-181a, or a nonsilencing control oligoribonucleotide, we asked whether the lenalidomide effect was mediated by miR-181a expression.…”

mentioning

confidence: 99%

Lenalidomide-mediated enhanced translation of C/EBPα-p30 protein up-regulates expression of the antileukemic microRNA-181a in acute myeloid leukemia

Hickey¹,

Schwind²,

Radomska³

et al. 2013

Blood

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• High miR-181a levels associate with CEBPA mutations and likely contribute to the favorable prognostic impact of these mutations in AML. • Lenalidomide induces CEBPA-dependent miR-181a expression and in turn increases sensitivity to chemo-therapy in AML blasts. Recently, we showed that increased miR-181a expression was associated with improved outcomes in cytogenetically normal acute myeloid leukemia (CN-AML). Interestingly, miR-181a expression was increased in CN-AML patients harboring CEBPA mutations, which are usually biallelic and associate with better prognosis. CEBPA encodes the C/EBP transcription factor. We demonstrate here that the presence of N-terminal CEBPA mutations and miR-181a expression are linked. Indeed, the truncated C/EBP-p30 isoform, which is produced from the N-terminal mutant CEBPA gene or from the differential translation of wild-type CEBPA mRNA and is commonly believed to have no transactivation activity, binds to the miR-181a-1 promoter and up-regulates the mi-croRNA expression. Furthermore, we show that lenalidomide, a drug approved for myelodysplastic syndromes and multiple myeloma, enhances translation of the C/EBP-p30 isoform, resulting in higher miR-181a levels. In xenograft mouse models, ectopic miR-181a expression inhibits tumor growth. Similarly, lenalidomide exhibits antitumori-genic activity paralleled by increased miR-181a expression. This regulatory pathway may explain an increased sensitivity to apoptosis-inducing chemotherapy in subsets of AML patients. Altogether, our data provide a potential explanation for the improved clinical outcomes observed in CEBPA-mutated CN-AML patients, and suggest that lenalidomide treatment enhancing the C/EBP-p30 protein levels and in turn miR-181a may sensitize AML blasts to chemotherapy. (Blood. 2013;121(1):159-169)

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“…One group showed that downregulation of miR-181a and subsequent upregulation of Bcl-2 in leukemia cells drove chemoresistance to Ara-C, 63 one of the most common drugs used in AML. The introduction of this miRNA into the cells increased chemosensitivity via apoptosis.…”

Section: The Future Of Therapy Related To Mirnamentioning

confidence: 99%

Current View of miRNA with Tumor Suppressor Function, Exploring MDS and AML as Models

Iverson

Galili

Ali

et al. 2014

Signal Transduction Insights

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ABSTRACT:Since the discovery of microRNAs (miRNAs) in 1993, their role in controlling a wide variety of complex and seminal cellular functions through control of gene expression continues to be elucidated. Studies of the past decade have shown that miRNAs are able to activate or suppress target genes that are key players in the molecular pathways found to be deregulated in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The ability of miRNAs to act as tumor suppressor genes has been demonstrated in a number of studies in both human samples and cell lines as well as in murine models of AML and MDS. The focus of this review will be to examine the complex interaction of specific miRNAs with genes that have been implicated in MDS/AML and which may eventually become therapeutically relevant.

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miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis

Cited by 52 publications

References 26 publications

MIR181Aregulates starvation- and rapamycin-induced autophagy through targeting ofATG5

MIR181Aregulates starvation- and rapamycin-induced autophagy through targeting ofATG5

Lenalidomide-mediated enhanced translation of C/EBPα-p30 protein up-regulates expression of the antileukemic microRNA-181a in acute myeloid leukemia

Current View of miRNA with Tumor Suppressor Function, Exploring MDS and AML as Models

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