miR‐22 regulates expression of oncogenic neuro‐epithelial transforming gene 1, <scp>NET</scp>1

Ahmad, Hafiz; Muiwo, Pamchui; Ramachandran, Suganthi S.; Pandey, Priyatama; Gupta, Yogendra Kumar; Kumar, Lalit; Kulshreshtha, Ritu; Bhattacharya, Alok

doi:10.1111/febs.12926

Cited by 32 publications

(23 citation statements)

References 41 publications

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“…3B). The up-regulated genes included: 1) genes involving in leukemogenesis (such as HHEX (Shields et al, 2016), NET1 (Ahmad et al, 2014)), tumorigenesis promoters (such as CDK6 , HOX family genes (Shah and Sukumar, 2010)), tyrosine kinase genes ( c-KIT , GRB10 (Kazi and Ronnstrand, 2013)); 2) Independent adverse prognostic factors in AML including WT1 , CXXC5 (Kuhnl et al, 2015), MSI2 (Byers et al, 2011), etc. ; 3) CD34 , which acts as a marker for hematopoietic progenitor cells; 4) genes correlating with drug-resistant in AML (such as IGFBP2 (Kuhnl et al, 2011) and ABCC1 (Xu et al, 2013a)).…”

Section: Resultsmentioning

confidence: 99%

“…RICTOR was targeted by miR-152 . HHEX (Shields et al, 2016), PBXIP1 (Xu et al, 2013b) and EZH1 (Xu et al, 2015) were all targets of miR-148a , NET1 (Ahmad et al, 2014) and HOXA4 (Zangenberg et al, 2009) were targeted by miR-22 ; MAP3K4 , ERG , ABL2 , CDK6 and CDK8 were targeted by miR-27a ; JAK1 , MAP3K3 , SRSF6 (Cohen-Eliav et al, 2013) and SRSF1 (Zou et al, 2012) were targeted by miR-708 . These discoveries perhaps helped to understand why CPT1A high could act as an adverse prognosticator.…”

Section: Resultsmentioning

confidence: 99%

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High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia

Shi

Jia

et al. 2016

EBioMedicine

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Carnitine palmitoyl transferase 1A (CPT1A) protein catalyzes the rate-limiting step of Fatty-acid oxidation (FAO) pathway, which can promote cell proliferation and suppress apoptosis. Targeting CPT1A has shown remarkable anti-leukemia activity. But, its prognostic value remains unclear in Acute Myeloid Leukemia (AML). In two independent cohorts of cytogenetically normal AML (CN-AML) patients, compared to low expression of CPT1A (CPT1Alow), high expression of CPT1A (CPT1Ahigh) was significantly associated with adverse outcomes, which was also shown in European Leukemia Network (ELN) Intermediate-I category. Multivariable analyses adjusting for known factors confirmed CPT1Ahigh as a high risk factor. Significant associations between CPT1Ahigh and adverse outcomes were further validated whether for all AML patients (OS: P = 0.008; EFS: P = 0.002, n = 334, no M3) or for National Comprehensive Cancer Network (NCCN) Intermediate-Risk subgroup (OS: P = 0.021, EFS: P = 0.024, n = 173). Multiple omics analysis revealed aberrant alterations of genomics and epigenetics were significantly associated with CPT1A expression, including up- and down-regulation of oncogenes and tumor suppressor, activation and inhibition of leukemic (AML, CML) and immune activation pathways, hypermethylation enrichments on CpG island and gene promoter regions. Combined with the previously reported anti-leukemia activity of CPT1A's inhibitor, our results proved CPT1A as a potential prognosticator and therapeutic target for AML.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia

Shi

Jia

et al. 2016

EBioMedicine

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“…To understand multiple chemoresistance mechanisms of miR-22-3p-regulated BCa, we first used the bioinformatic software miRDB and TargetScan to perform bioinformatic analysis. We studied 240 target genes that appeared simultaneously in the two predictive softwares and some target genes of miR-22-3p that have been studied; these target genes of miR-22-3p include TET2 (18), NET1 (25), CD147 (20), Tcf7 (26), VE-cadherin (27), TGFβR (28), KDM3A (21), CD151 (16), MTHFR (15), HMGB1 (22), Sp1 (29) and SRF (30) (only some of the genes appeared among the 240 target genes predicted by the website). These genes were detected by RNA-seq in 5637 and H-bc cell lines to identify the target of miR-22-3p in BCa.…”

Section: Mir-22-3p Levels Were Higher In Chemoresistant (H-bc)mentioning

confidence: 99%

miR‑22‑3p enhances multi‑chemoresistance by targeting NET1 in bladder cancer cells

et al. 2018

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With the discovery of new chemotherapeutic drugs, chemotherapy becomes increasingly valuable. However, the resistance of tumor cells to chemotherapeutic agents significantly limits the effectiveness and causes chemotherapy failure. MicroRNAs have been shown to regulate drug resistance in many types of cancer. In the present study, we measured the chemosensitivity of five bladder cancer (BCa) cell lines to seven commonly used chemotherapeutic drugs by Vita‑Blue assay. We then identified the most sensitive (5637) and most tolerant cell lines (H‑bc) and conducted a multi‑group test. This test included expression group analyses of coding and non‑coding genes (miR‑omic and RNA‑seq). Based on our analyses, we selected miR‑22‑3p as a target. We then determined its own target gene [neuroepithelial cell transforming 1 (NET1)] by bioinformatic analysis and confirmed this finding by TaqMan‑quantitative reverse transcription polymerase chain reaction (qRT‑PCR), western blot analysis and luciferase reporter assay. The effect of miR‑22‑3p on BCa multi‑chemoresistance was also determined by transfecting cells with the miR‑22‑3p‑mimic or miR‑22‑3p‑antagomiR. We assessed the involvement of NET1 in BCa chemoresistance by siRNA‑mediated NET1 inhibition or pINDUCER21‑enhanced green fluorescent protein‑NET1‑mediated overexpression. Plate colony formation and apoptosis assays were conducted to observe the effects of miR‑22‑3p and NET1 on BCa chemoresistance. In conclusion, our results suggest that miR‑22‑3p promotes BCa chemoresistance by targeting NET1 and may serve as a new prognostic biomarker for BCa patients.

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“…Anmad et al report that miR-22 is downregulated in peripheral blood mononuclear cells derived from chronic myeloid leukemia (CML) patients and in CML cell line K562 [24]. And, overexpression of miR-22 inhibits proliferation and alteration in cell cycle of K562 cells by regulating neuro-epithelial transforming gene 1 (NET1).…”

Section: Cell Physiolmentioning

confidence: 99%

MiR-22 may Suppress Fibrogenesis by Targeting TGFβR I in Cardiac Fibroblasts

Hong

Cao²,

Wang³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure, but the mechanisms undelying cardiac fibrosis remained unknown. microRNAs (miRNAs) are novel mechanisms leading to fibrotic diseases, including cardiac fibrosis. Previous studies revealed that miR-22 might be a potential target. However, the roles and mechanisms of miR-22 in cardiac fibrosis remained ill defined. The present study thus addressed the impact of miR-22 in cardiac fibrosis. Methods: After seven days following coronary artery occlusion in mice, tissues used for histology were collected and processed for Masson's Trichrome staining. In addition, cardiac fibroblasts were transfected with mimics and inhibitors of miR-22 using Lipofectamin 2000, and luciferase activity was measured in cell lysates using a luciferase assay kit. Western blotting was used to detect the expression of collagen1, α-SMA and TGFβRI proteins levels, and real time-PCR was employed to measure the Col1α1, Col3α1, miR-22 and TGFβRI mRNA levels. Results: In this study, we found that miR-22 was dynamically downregulated following MI induced by permanent ligation of the left anterior descending coronary artery for 7 days, an effect paralleled by significant collagen deposition. Inhibition of miR-22 with AMO-22 resulted in increased expression of Col1α1, Col3α1 and fibrogenesis in cultured cardiac fibroblasts. Conversely, overexpression of miR-22 in cultured cardiac fibroblasts significantly abrogated angiotensin II-induced collagen formation and fibrogenesis. Furthermore, we found that TGFβRI is a direct target for miR-22, and downregulation of TGFβR may have mediated the antifibrotic effect of miR-22. Conclusion: Our data clearly demonstrate that miR-22 acts as a novel negative regulator of angiotensin II-induced cardiac fibrosis by suppressing the expression of TGFβRI in the heart and may represent a new potential therapeutic target for treating cardiac fibrosis.

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miR‐22 regulates expression of oncogenic neuro‐epithelial transforming gene 1, NET1

Cited by 32 publications

References 41 publications

High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia

High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia

miR‑22‑3p enhances multi‑chemoresistance by targeting NET1 in bladder cancer cells

MiR-22 may Suppress Fibrogenesis by Targeting TGFβR I in Cardiac Fibroblasts

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