MicroRNA-221 sensitizes chronic myeloid leukemia cells to imatinib by targeting STAT5

Jiang, Xiaoxiao; Cheng, Yuejuan; Hu, Chaojie; Zhang, Aimei; Ren, Yingli; Xu, Xiaojun

doi:10.1080/10428194.2018.1543875

Cited by 29 publications

(22 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it is confirmed that miR-221 can modulate breast carcinoma cell proliferation through STAT5 signaling pathway. 25 This result is similar to ours that SOCS2-AS regulated the expression of STAT5 through miR-221.…”

Section: Discussionsupporting

confidence: 89%

<p>Long Noncoding RNA SOCS2-AS Promotes Leukemogenesis in FLT3-ITD+ Acute Myeloid Leukemia Through miRNA-221</p>

Zhang¹,

Huo²

2020

OTT

View full text Add to dashboard Cite

Background: LncRNAs play an important role in tumorigenesis and development in tumors, but the function of lncRNA SOCS2-AS in acute myeloid leukemia (AML) is unknown. Materials and Methods: In the present study, we used RT-PCR to detect the expression of SOCS2-AS in FLT3-ITD+, FLT3-ITD-AML patients and different AML cell lines. The colony formation and CCK-8 assay were performed to analyze the proliferation ability, and the flow cytometry was performed to analyze the capacity of apoptosis in Molm-13 and MV4-11 cells. The Western blot was applied to detect the expression of STAT5 and p-STAT5. The RNA pulldown and luciferase activity were used to investigate the interaction between SOCS2-AS and miR-221. Results: The results indicate that SOCS2-AS shows overexpression in FLT3-ITD+ AML patients compared to FLT3-ITD-AML patients. Si-SOCS2-AS can inhibit the proliferation, boost the apoptosis and induce the cycle arrest in Molm-13 cells, and SOCS2-AS overexpression promotes proliferation and colony formation in MV4-11 cells. The miR-221 shows overexpression in FLT3-ITD+ AML patients compared to FLT3-ITD-AML patients. And the expression level of miR-221 and SOCS2-AS shows negative correlation in FLT3-ITD+ AML patients. Functionally, SOCS2-AS could be interacted with miR-221 in AML cells. After SOCS2-AS knockdown, the phosphorylation level of STAT5 was significantly decreased. Moreover, miR-221 inhibitor can rescue the viability in cells after si-SOCS2-AS transfection. And it is stated that SOCS2-AS regulates the STAT5 signal transduction pathway with sponging miR-221. Conclusion: In conclusion, this study confirms the molecular mechanism of SOCS2-AS in AML by targeting the miR-221/STAT5 signaling pathway. This indicates SOCS2-AS may serve as a potential therapeutic target for the treatment of AML.

show abstract

Section: Discussionsupporting

confidence: 89%

<p>Long Noncoding RNA SOCS2-AS Promotes Leukemogenesis in FLT3-ITD+ Acute Myeloid Leukemia Through miRNA-221</p>

Zhang¹,

Huo²

2020

OTT

View full text Add to dashboard Cite

show abstract

“…A total of 46 apoptosis-related proteins were detected and 20 DEPs were screened out and enriched with KEGG, and these proteins were found to play a role in 12 regulatory pathways, including the apoptosis signaling pathway, the p53 signaling pathway and the tumor necrosis factor signaling pathway. The authors previously demonstrated that the p53 signaling pathway that regulates redox status plays an essential role in IM resistance (17). The study had revealed that IGFBP-1 acts as a negative regulator of BAK-dependent apoptosis and its expression is involved in the transcriptional and mitochondrial functions of the p53 tumor suppressor protein (35).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the K562/G cells were cultured in the continuous presence of 1 µmol/l imatinib. The methods for the detection of cell drug resistance, were as mentioned in an earlier study (17). The K562/G cells exhibited significantly higher resistance to IM, with >50-fold increase of the IC50 value, compared with K562 cells.…”

Section: Methodsmentioning

confidence: 99%

Insulin‑like growth factor‑binding proteins play a significant role in the molecular response to imatinib in chronic myeloid leukemia patients

et al. 2019

Self Cite

View full text Add to dashboard Cite

Imatinib (IM) is successfully used in the majority of patients with chronic myeloid leukemia (CML), but some patients develop resistance to drug treatment. Insufficient apoptosis results in uncontrolled cell proliferation, which is closely associated with the occurrence of drug resistance. Therefore, it is crucial to identify new biomarkers related to drug resistance. This aim of the present study was to investigate the profile of apoptosis-related proteins in K562 and K562/G (IM-resistant K562 cells) cells, in order to identify new biomarkers. A human apoptosis antibody array was used to screen 46 proteins in the two cells lines, among which 20 proteins were found to be differentially expressed between K562 and K562/G cells. The major proteins included secreted caspase-8, insulin-like growth factor-binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, caspase-3 and p27. IGFBP-1 IGFBP-2 and IGFBP-3 were selected for the follow-up study. Subsequently, reverse transcription-quantitative PCR analysis and western blotting were used to detect the expression levels of the IGFBPs. The results revealed that the expression levels of IGFBP-2 and IGFBP-3 in K562/G cells were significantly decreased compared with those in K562 cells, whereas the IGFBP-1 level was higher. Moreover, no significant correlation was observed between IGFBP-1 or IGFBP-2 and the level of the BCR-ABL fusion protein, whereas decreasing IGFBP-3 levels were associated with increasing BCR-ABL levels. These results suggested that IGFBP-1, IGFBP-2 and IGFBP-3 could be useful novel biomarkers for IM resistance in CML.

show abstract

“…In chronic myeloid leukaemia (CML) cell lines, increased levels of miRNA-221 were also found to enhance response to treatment, in this case restoring sensitivity to imatinib in the resistant cell line K562/G via repression of STAT5 [108]. A reduction in expression of miRNA-221 was also measured in peripheral blood mononuclear cells (PBMC) from patients with treatment failure when compared with patients with optimal responses [108].…”

Section: Mirna-221 and -222 Influence Treatment Sensitivity In Leukaemiamentioning

confidence: 99%

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

Withers

Dewhurst

Hammond

et al. 2020

ncRNA

View full text Add to dashboard Cite

Adipose tissue is an endocrine organ, capable of regulating distant physiological processes in other tissues via the release of adipokines into the bloodstream. Recently, circulating adipose-derived microRNAs (miRNAs) have been proposed as a novel class of adipokine, due to their capacity to regulate gene expression in tissues other than fat. Circulating levels of adipokines are known to be altered in obese individuals compared with typical weight individuals and are linked to poorer health outcomes. For example, obese individuals are known to be more prone to the development of some cancers, and less likely to achieve event-free survival following chemotherapy. The purpose of this review was twofold; first to identify circulating miRNAs which are reproducibly altered in obesity, and secondly to identify mechanisms by which these obesity-linked miRNAs might influence the sensitivity of tumors to treatment. We identified 8 candidate circulating miRNAs with altered levels in obese individuals (6 increased, 2 decreased). A second literature review was then performed to investigate if these candidates might have a role in mediating resistance to cancer treatment. All of the circulating miRNAs identified were capable of mediating responses to cancer treatment at the cellular level, and so this review provides novel insights which can be used by future studies which aim to improve obese patient outcomes.

show abstract

MicroRNA-221 sensitizes chronic myeloid leukemia cells to imatinib by targeting STAT5

Cited by 29 publications

References 45 publications

<p>Long Noncoding RNA SOCS2-AS Promotes Leukemogenesis in FLT3-ITD+ Acute Myeloid Leukemia Through miRNA-221</p>

<p>Long Noncoding RNA SOCS2-AS Promotes Leukemogenesis in FLT3-ITD+ Acute Myeloid Leukemia Through miRNA-221</p>

Insulin‑like growth factor‑binding proteins play a significant role in the molecular response to imatinib in chronic myeloid leukemia patients

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

Contact Info

Product

Resources

About