MiRNA profiling in B non‐Hodgkin lymphoma: a <i>MYC</i>‐related miRNA profile characterizes Burkitt lymphoma

Robertus, Jan-Lukas; Kluiver, Joost; Weggemans, Callista; Harms, Geert; Reijmers, Rogier M.; Swart, Yolanthe; Kok, Klaas; Rosati, S.; Schuuring, Ed; Imhoff, Gustaaf van; Pals, Steven T.; Kluin, Philip M.; Berg, Anke van den

doi:10.1111/j.1365-2141.2010.08111.x

Cited by 66 publications

(65 citation statements)

References 10 publications

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“…Mounting evidence showed that miR-494, considered to be a tumor-suppressing miRNA, suppressed the cell proliferation in many solid tumors including squamous cell carcinoma of the head and neck, B-Cell Lymphomas and so on (Chang et al, 2008;Robertus et al, 2010). However, no data to date are available about the association of miR-494 with gastric cancer .…”

Section: Discussionmentioning

confidence: 94%

Cinobufacin Suppresses Cell Proliferation via miR-494 in BGC-823 Gastric Cancer Cells

Zhou

Chen²,

Shen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Cinobufacin is used clinically to treat patients with many solid malignant tumors. However, the mechanisms underlying action remain to be detailed. Our study focused on miRNAs involved in cinobufacin inhibition of GC cell proliferation. miRNA microarray analysis and real time PCR identified miR-494 as a significant cinobufacinassociated miRNA. In vivo, ectopic expression of miR-494 inhibited the proliferation and induced apoptosis of BGC-823 cells on CCK-8 and flow cytometry analysis. Further study verified BAG-1 (anti-apoptosis gene) to bea target of miR-494 by luciferase reporter assay and Western blotting. In summary, our study demonstrated that cinobufacin may inhibit the proliferation and promote the apoptosis of BGC-823 cells. Cinobufacin-associated miR-494 may indirectly be involved in cell proliferation and apoptosis by targeting BAG-1, pointing to use as a potential molecular target of cinobufacin in gastric cancer therapy.

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Section: Discussionmentioning

confidence: 94%

Cinobufacin Suppresses Cell Proliferation via miR-494 in BGC-823 Gastric Cancer Cells

Zhou

Chen²,

Shen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…In search of potentially involved miRNAs, we identified conserved binding sites for the MYC‐suppressed miRNAs miR‐15a/16‐1, ‐22, ‐23ab ‐26ab, ‐29abc, ‐30e‐5p, and ‐195 in the 3′untranslated region (3′UTR) of the TSC1 mRNA by using the TargetScan algorithm (http://www.targetscan.org). Importantly, those miRNAs are direct MYC targets and were found to be among the suppressed miRNAs in high MYC expressing BL patient samples compared to B cells from hyperplastic tonsils or samples from patients with MYC translocation negative non‐Hodgkin lymphomas (NHLs), including mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL) (Robertus et al , 2010; Table EV1). Overexpression of single miRNAs in HEK293T cells revealed that miR‐15a, miR‐22, and miR‐23a strongly suppressed TSC1 and increased P‐S6K with miR‐15a having the strongest effect on inducing phosphorylation of S6K (Fig EV5A).…”

Section: Resultsmentioning

confidence: 99%

Tuberous sclerosis complex is required for tumor maintenance in MYC‐driven Burkitt's lymphoma

et al. 2018

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The tuberous sclerosis complex (TSC) 1/2 is a negative regulator of the nutrient‐sensing kinase mechanistic target of rapamycin complex (mTORC1), and its function is generally associated with tumor suppression. Nevertheless, biallelic loss of function of TSC1 or TSC2 is rarely found in malignant tumors. Here, we show that TSC1/2 is highly expressed in Burkitt's lymphoma cell lines and patient samples of human Burkitt's lymphoma, a prototypical MYC‐driven cancer. Mechanistically, we show that MYC induces TSC1 expression by transcriptional activation of the TSC1 promoter and repression of miR‐15a. TSC1 knockdown results in elevated mTORC1‐dependent mitochondrial respiration enhanced ROS production and apoptosis. Moreover, TSC1 deficiency attenuates tumor growth in a xenograft mouse model. Our study reveals a novel role for TSC1 in securing homeostasis between MYC and mTORC1 that is required for cell survival and tumor maintenance in Burkitt's lymphoma. The study identifies TSC1/2 inhibition and/or mTORC1 hyperactivation as a novel therapeutic strategy for MYC‐driven cancers.

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“…S8). Other studies reported the decreased expression of miR-494 in lymphoma and squamous cell carcinoma of the head and neck in miRNA microarray profiling studies (25,26); however, the direct relationship between this decreased expression and tumor-related gene expression has not been Figure 4. GIST cell proliferation is inhibited by miR-494.…”

Section: Apoptosis and Cell-cycle Analysis After Mir-494 Overexpressimentioning

confidence: 99%

MicroRNA-494 Downregulates KIT and Inhibits Gastrointestinal Stromal Tumor Cell Proliferation

Kim

Park

Kim

et al. 2011

Clinical Cancer Research

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Purpose: Gain-of-function mutations and KIT overexpression are well-known tumorigenesis mechanisms in gastrointestinal stromal tumors (GIST). This study aimed to discover microRNAs (miRNA) that target KIT and reveal the relationship between the discovered miRNAs and KIT expression in GISTs.Experimental Design: Fresh-frozen GISTs from 31 patients were used to confirm the relationship between miR-494 and KIT expression using quantitative reverse transcription-PCR to assess miR-494 expression levels and Western blotting to assess KIT protein expression levels. A luciferase assay was conducted for the target evaluation. The functional effects of miR-494 on GIST882 cells (GIST cell line with activating KIT mutation) were validated by a cell proliferation assay and fluoresce-activated cell sorting analysis.Results: An inverse relationship was found between the expression levels of miR-494 and KIT in GISTs (r ¼ À0.490, P ¼ 0.005). The direct targeting of KIT by miR-494 was shown by the reduction in KIT expression after miR-494 overexpression and the increase in KIT expression after inhibiting endogenous miR-494 expression. We showed that miR-494 regulates KIT by binding two different seed match sites. Induced miR-494 overexpression in GIST882 reduced the expression of downstream molecules in KIT signaling transduction pathways, including phospho-AKT and phospho-STAT3. Finally, miR-494 overexpression provoked apoptosis and inhibited GIST cell growth, which were accompanied by changes in G 1 and S phase content.Conclusion: Our findings indicate that miR-494 is a negative regulator of KIT in GISTs and overexpressing miR-494 in GISTs may be a promising approach to GIST treatment.

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MiRNA profiling in B non‐Hodgkin lymphoma: a MYC‐related miRNA profile characterizes Burkitt lymphoma

Cited by 66 publications

References 10 publications

Cinobufacin Suppresses Cell Proliferation via miR-494 in BGC-823 Gastric Cancer Cells

Cinobufacin Suppresses Cell Proliferation via miR-494 in BGC-823 Gastric Cancer Cells

Tuberous sclerosis complex is required for tumor maintenance in MYC‐driven Burkitt's lymphoma

MicroRNA-494 Downregulates KIT and Inhibits Gastrointestinal Stromal Tumor Cell Proliferation

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