MicroRNA-30a Sensitizes Tumor Cells to cis-Platinum via Suppressing Beclin 1-mediated Autophagy

Zou, Zhenyou; Wu, Ling-Ling; Ding, Hanying; Wang, Yan; Zhang, Yaqin; Chen, Xuejiao; Chen, Xi; Zhang, Chenyu; Zhang, Qipeng; Zen, Ke

doi:10.1074/jbc.m111.307405

Cited by 170 publications

(135 citation statements)

References 43 publications

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“…26 miR-30a sensitizes tumor cells to cis-platinum via suppressing Beclin 1-mediated autophagy. 27 miR-204 regulates autophagy through LC3-II. 28 It remains largely unknown as to how autophagy is regulated by miRNAs.…”

mentioning

confidence: 99%

Autophagic program is regulated by miR-325

Fang

et al. 2014

Cell Death Differ

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Autophagy is required for the maintenance of cardiomyocytes homeostasis. However, the abnormal autophagy could lead to the development of heart failure. Autophagy is enhanced during myocardial ischemia/reperfusion; it remains to elucidate the molecular regulation of autophagy. We report here that miR-325, ARC and E2F1 constitute an axis that regulates autophagy. Our results showed that miR-325 expression is upregulated upon anoxia/reoxygenation and ischemia/reperfusion. Cardiomyocytespecific overexpression of the miR-325 potentiates autophagic responses and myocardial infarct sizes, whereas knockdown of miR-325 inhibited autophagy and cell death. We searched for the downstream mediator of miR-325 and identified that ARC is a target of miR-325. ARC transgenic mice could attenuate autophagy and myocardial infarction sizes upon pressure-overloadinduced heart failure, whereas ARC null mice exhibited an increased autophagic accumulation in the heart. The suppression of ARC by miR-325 led to its inability to repress autophagic program. In exploring the molecular mechanism by which miR-325 expression is regulated, our results revealed that the transcription factor E2F1 contributed to promote miR-325 expression. E2F1 null mice demonstrated reduced autophagy and myocardial infarction sizes upon ischemia/reperfusion. Our present study reveals a novel autophagic regulating model that is composed of E2F1, miR-325 and ARC. Modulation of their levels may provide a new approach for tackling cardiac failure.

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mentioning

confidence: 99%

Autophagic program is regulated by miR-325

Fang

et al. 2014

Cell Death Differ

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“…16,17 miR-30a also sensitizes tumor cells to cisplatin by suppressing beclin-1-mediated autophagy. 18 These results support a new treatment development strategy of overcoming chemoresistance by modulating miRNA-mediated autophagy. Recently, more miRNAs have been reported to be mediators of the autophagic process.…”

Section: Mirnas Involved In Regulating the Expression Of Key Autophagmentioning

confidence: 63%

“…miR-30a also enhances the tumor cell apoptosis induced by cisplatin through suppressing belcin-1-mediated autophagy. 18 miR-221/222 expression on the other hand has been shown to increase tamoxifen resistance in breast cancer by decreasing levels of p27. 64 Similarly, miR-21 expression level autophagy regulation is complex.…”

Section: Therapeutic Potential Of Mirnas and Autophagic Pathwaymentioning

confidence: 99%

MicroRNA

Zhai

Fesler

2013

Cell Cycle

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“…42,48 Human MIR101, MIR30A, and MIR221 are some of the key miRNAs that have proved their therapeutic potential against cancer. 35,46,47 These therapeutic approaches involve usage of miR-mimics or anti-miRs as potential therapeutic molecules for anticancer drug development. 49 The role of miRNAs in controlling intracellular pathogens such as Mycobacterium and Salmonella is well documented and several microRNAs including MIR30A and MIR155 play key roles in regulating autophagy process by targeting several key molecules regulating the process of autophagy during the course of infection in human macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…17,32,33 The regulatory role of MIR30 family members in downregulation of several genes (e.g., BECN1) involved in autophagy process in cancer cells and infection models has been reported earlier. [34][35][36] Figure 2. Induction of the Leishmania-specific MIR30 family of miRNAs.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA expression profiling ofLeishmania donovani-infected host cells uncovers the regulatory role of MIR30A-3p in host autophagy

et al. 2016

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Leishmania is an obligate intracellular parasite that replicates inside phagolysosomes or parasitophorous vacuoles (PV) of the monocyte/macrophage lineage. It reprograms macrophages and produces a metabolic state conducive to successful infection and multiplication. MicroRNAs (miRNAs), a class of small 22 to 24 nucleotide noncoding regulatory RNAs alter the gene expression and consequently proteome output by targeting mRNAs, may play a regulatory role in modulating host cell functions. In the present study, we demonstrate the novel regulatory role of host microRNA, MIR30A-3p in modulation of host cell macroautophagy/autophagy after infection with L. donovani. Our in vitro studies showed that MIR30A-3p expression was significantly enhanced after L. donovani infection in a time-dependent manner. Transient transfection with a MIR30A-3p inhibitor followed by L. donovani infection promoted the autophagic response and decreased the intracellular parasite burden in both THP-1 cells and human monocytederived macrophages (HsMDM). BECN1/Beclin 1, the mammalian ortholog of yeast Vps30/Atg6, is a key autophagy-promoting protein that plays a key role in the regulation of cell death and survival. We report BECN1-dependent modulation of host cell autophagy in response to L. donovani infection. Pretreatment of L. donovani-infected macrophages with the MIR30A-3p mimic decreased and with antagomir increased the expression of BECN1 protein. We demonstrate that BECN1 is a potential target of MIR30A-3p and this miRNA negatively regulates BECN1 expression. Our present study reveals for the first time a novel role of MIR30A-3p in regulating autophagy-mediated L. donovani elimination by targeting BECN1. The present study has significant impact for the treatment of visceral leishmaniasis.

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MicroRNA-30a Sensitizes Tumor Cells to cis-Platinum via Suppressing Beclin 1-mediated Autophagy

Cited by 170 publications

References 43 publications

Autophagic program is regulated by miR-325

Autophagic program is regulated by miR-325

MicroRNA

MicroRNA expression profiling ofLeishmania donovani-infected host cells uncovers the regulatory role of MIR30A-3p in host autophagy

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