MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

Xiao, Yi; Deng, Taoran; Su, Changliang; Shang, Zhen

doi:10.3892/ol.2017.6076

Cited by 43 publications

(31 citation statements)

References 37 publications

(42 reference statements)

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“…miRNAs are a subset of small noncoding RNAs that control gene expression in a site-specific manner (15). Accumulating evidence has identified the distinct expression patterns and biological functions of miRNAs in biological processes, including cell differentiation, apoptosis, and metabolism (16).…”

mentioning

confidence: 99%

Role of Circular RNA DLEU2 in Human Acute Myeloid Leukemia

Wen

Han

et al. 2018

Molecular and Cellular Biology

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In the current study, we were interested in exploring the molecular mechanism of circular RNA DLEU2 (circRNA-DLEU2) (hsa_circ_0000488) and microRNA 496 (miR-496), as well as PRKACB, in human acute myeloid leukemia (AML) cell activities. The RNA expression levels of circRNA-DLEU2, hsa-miR-496, and PRKACB were assessed by quantitative real-time PCR (qRT-PCR). The proliferation and apoptosis abilities of the cells were determined by CCK8 assay and flow cytometry analysis. Target relationships between circRNA-DLEU2 and miR-496, as well as PRKACB, were analyzed by luciferase reporter assay and probe assay. Immunoblotting assays were used to detect the protein expression level of PRKACB. We also did experiments to observe tumor formation after overexpression of circRNA-DLEU2. Our data showed that circRNA-DLEU2 was upregulated in AML tissues and cells, which promoted AML cell proliferation and inhibited cell apoptosis. circRNA-DLEU2 promoted AML tumor formation miR-496 was inhibited by circRNA-DLEU2 and was downregulated in AML tissues. circRNA-DLEU2 inhibited miR-496 expression and promoted PRKACB expression. miR-496 antagonized the effects of PRKACB on MOLM-13 cell proliferation and apoptosis. Collectively, circRNA-DLEU2 accelerated human AML by suppressing miR-496 and promoting PRKACB expression.

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confidence: 99%

Role of Circular RNA DLEU2 in Human Acute Myeloid Leukemia

Wen

Han

et al. 2018

Molecular and Cellular Biology

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“…In leukaemia cells, it has been demonstrated that several types of microRNAs exert roles. For example, MicroRNA 217 inhibits leukaemia cell proliferation and enhances chemosensitivity . Downregulation of miR‐224 contribute to cell survival and chemoresistance in chronic myeloid leukaemia cells .…”

Section: Discussionmentioning

confidence: 99%

“…For example, MicroRNA 217 inhibits leukaemia cell proliferation and enhances chemosensitivity. 19 Downregulation of miR-224 contribute to cell survival and chemoresistance in chronic myeloid leukaemia cells. 20 There are some reports indicating the correlation between HoxA9 and microRNA expression.…”

Section: Discussionmentioning

confidence: 99%

HOXA9 is critical in the proliferation, differentiation, and malignancy of leukaemia cells both in vitro and in vivo

Chen

Yu²,

et al. 2017

Cell Biochemistry & Function

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Progress in the understanding of the molecular mechanism for acute myeloid leukaemia is of great significance to generate new potential targets for treatment. Recent studies showed that HOXA9, a homeodomain-containing transcription factor, is commonly deregulated in acute leukaemia. In this study, we elucidated the direct correlation between HoxA9 expression and progression of leukaemia using 2 different types of leukaemia cells HL-60 and MOLT-3. The HoxA9 expression level was decreased in leukaemia cells with the treatment of all-trans retinoic acid or arsenic trioxide (As O ). Downregulation of HoxA9 could impair the proliferation and promote the leukaemia cell death. HoxA9 silencing also potentiated the differentiation of leukaemia cells, and in vivo studies demonstrated that HoxA9 downregulation could interfere the tumour growth. Interestingly, HoxA9 silencing also led to the alteration in miRNA expression, mediating the promoting effect on the leukaemia cell differentiation. Therefore, this work provided a promising and potentially efficient target to leukaemia treatment, indicating that HoxA9 is likely to be an ideal candidate in the gene therapy against acute myeloid leukaemia. In this study, we elucidated the critical role of HoxA9 in the proliferation and differentiation of leukaemia cells both in vitro and in vivo. The effect of HoxA9 modulation was correlated with the clinical effect of all-trans retinoic acid and As O . Furthermore, HoxA9 also regulated the miRNA expression, controlling the leukaemia cell differentiation. Therefore, this work provided new insights into molecular mechanism underlying the leukaemia treatment, potentially putting forward a brand new target to the gene therapy against leukaemia.

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“…Group 1 characterized with high level of expression of sncRNAs, which associated with sensitivity to therapy. This group members are miRNA-181a, b; let-7f, miRNA-9*, miRNA-96, miRNA-135a, miRNA-409, miRNA-10, miRNA29b and miRNA-217 [72,73,[97][98][99][100]. Group 1 members act through activation of cellular differentiation, inhibition of leukemic cells proliferation and survival, regulation of cell cycle, inducing of apoptosis and suppression of migration and invasion.…”

Section: Sncrnas As Markers Of Therapeutic Resistance or Sensitivity mentioning

confidence: 99%

“…It targets KRAS regulator of signaling links from extracellular space to the nucleus. KRAS connects multiple upstream signals to various downstream signaling pathways [97].…”

Section: Sncrnas As Markers Of Therapeutic Resistance or Sensitivity mentioning

confidence: 99%

Small Non-Coding RNAs in Regulation of Course and Therapeutic Efficacy in Acute Myeloid Leukemia

Klimenko¹

2018

Myeloid Leukemia

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Small non-coding RNAs (sncRNAs) are small regulatory molecules, which play key roles in fine-tune of all cell functions. In late 1970s and early 1980s, it was first determined that non-coding RNAs contribute to the cellular regulatory processes. The kingdom of sncRNAs is very numerous and it is clear that functions of different members of this family is different from each other and may be involved in normal and pathologic processes in cell. Recently it was investigated that sncRNAs and long non-coding RNAs play roles in cellular differentiation, proliferation, metabolic processes, bioenergetic regulation, cell death and inter-cellular communications, etc. In embryos, non-coding RNAs control maternal-zygotic transition, the maintenance of pluripotency, the pattering of the body axes, the specification and differentiation of cell types and morphogenesis of organs. Development of hematologic malignancies in humans, their course and regulation of resistance and sensitivity of tumorous cells to therapy are under the control of sncRNAs.

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MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

Cited by 43 publications

References 37 publications

Role of Circular RNA DLEU2 in Human Acute Myeloid Leukemia

Role of Circular RNA DLEU2 in Human Acute Myeloid Leukemia

HOXA9 is critical in the proliferation, differentiation, and malignancy of leukaemia cells both in vitro and in vivo

Small Non-Coding RNAs in Regulation of Course and Therapeutic Efficacy in Acute Myeloid Leukemia

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