The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma

Shimizu, Satoshi; Takehara, Tetsuo; Hikita, Hayato; Kodama, Tatsuhiko; Miyagi, Takuya; Hosui, Atsushi; Tatsumi, Tomohide; Ishida, Hisashi; Noda, Takehiro; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki; Hayashi, Norio

doi:10.1016/j.jhep.2009.12.024

Cited by 321 publications

(240 citation statements)

References 37 publications

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“…Previous measurements of miRNAs in liver samples revealed that let-7a, miR-16, miR-20, miR-21, and miR-22 were present at 700, 3 890, 130, 4 450, and 310 copies per cell, respectively [43], while miR-181a was expressed at 810 copies per cell in DP thymocytes [44] and miR-223 and miR-451 were 828 and 1 972 copies per cell in CD34(+)/CD133(−) cells [45]. It has been widely demonstrated that miRNAs expressed at these concentrations are biologically active [46][47][48][49]. We calculated the amount of MIR168a that was detected in 1 mg of total liver RNA.…”

Section: Ago2-associated Mature Mir168a In Mvs Is the Functional Formmentioning

confidence: 99%

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

et al. 2011

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Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.

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Section: Ago2-associated Mature Mir168a In Mvs Is the Functional Formmentioning

confidence: 99%

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

et al. 2011

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“…Recent studies have shown that let-7 is involved in various biological processes and likely as a tumor suppressor (40). In addition, it was recently reported that the antiapoptotic protein BCL-XL is also a target of let-7a in human hepatocellular carcinoma (41). This information led to our hypothesis that let-7a is responsible for CXCR4 signaling-mediated chemoresistance in AML cells.…”

Section: Discussionmentioning

confidence: 90%

CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia

Chen¹,

Jácamo²,

Konopleva³

et al. 2013

J. Clin. Invest.

171

130

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We examined the role of microRNAs (miRNAs) in targeting the stromal-derived factor 1α/CXCR4 (SDF-1α/ CXCR4) axis to overcome chemoresistance of AML cells. Microarray analysis of OCI-AML3 cells revealed that the miRNA let-7a was downregulated by SDF-1α-mediated CXCR4 activation and increased by CXCR4 inhibition. Overexpression of let-7a in AML cell lines was associated with decreased c-Myc and BCL-XL protein expression and enhanced chemosensitivity, both in vitro and in vivo. We identified the transcription factor Yin Yang 1 (YY1) as a link between SDF-1α/CXCR4 signaling and let-7a, as YY1 was upregulated by SDF-1α and downregulated by treatment with a CXCR4 antagonist. ChIP assay confirmed the binding of YY1 to unprocessed let-7a DNA fragments, and treatment with YY1 shRNA increased let-7a expression. In primary human AML samples, high CXCR4 expression was associated with low let-7a levels. Xenografts of primary human AML cells engineered to overexpress let-7a exhibited enhanced sensitivity to cytarabine, resulting in greatly extended survival of immunodeficient mice. Based on these data, we propose that CXCR4 induces chemoresistance by downregulating let-7a to promote YY1-mediated transcriptional activation of MYC and BCLXL in AML cells.

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“…In hepatocelluar carcinoma, the let-7 family of miRNAs including Let-7c has been reported to potentiate sorafenib-induced apoptosis by inhibiting Bcl-xL expression (31). Bcl-xL is an antiapoptotic member of the Bcl-2 family comprising a group of structurally related proteins that play a fundamental role in the regulation of the intrinsic pathway by controlling mitochondrial membrane permeability and the release of the proapoptotic factor (32).…”

Section: Discussionmentioning

confidence: 99%

Let-7c Governs the Acquisition of Chemo- or Radioresistance and Epithelial-to-Mesenchymal Transition Phenotypes in Docetaxel-Resistant Lung Adenocarcinoma

Cui

Huang

Chen

et al. 2013

Molecular Cancer Research

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MicroRNA (miRNA) expression and functions have been reported to contribute to phenotypic features of tumor cells. Although targets and functional roles for many miRNAs have been described in lung adenocarcinoma (LAD), their pathophysiologic roles in phenotypes of chemoresistant LAD cells are still largely unclear. Previously, docetaxel (DTX)-resistant LAD cell lines (SPC-A1/DTX and H1299/DTX) were established by our laboratory and displayed chemo-or radioresistance and mesenchymal features with enhanced invasiveness and motility. Unbiased miRNA profiling indicated that let-7c (MIRLET7C) was significantly downregulated in SPC-A1/DTX cells. Ectopic let-7c expression increased the in vitro and in vivo chemo-or radiosensitivity of DTX-resistant LAD cells through enhanced apoptosis, reversal of epithelial-tomesenchymal phenotypes, and inhibition of in vivo metastatic potential via inactivation of Akt phosphorylation, whereas a let-7c inhibitor decreased the chemo

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The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma

Cited by 321 publications

References 37 publications

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia

Let-7c Governs the Acquisition of Chemo- or Radioresistance and Epithelial-to-Mesenchymal Transition Phenotypes in Docetaxel-Resistant Lung Adenocarcinoma

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