microRNAs and death receptors

Park, Sun Mi; Marynen, Peter

doi:10.1016/j.cytogfr.2008.04.011

Cited by 34 publications

(37 citation statements)

References 114 publications

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“…MicroRNAs are known to play critical roles in development, cell proliferation, and other fundamental cellular processes (Cimmino et al 2005;Rougvie 2005;Gu and Iyer 2006;Johnson et al 2007;Park and Peter 2008). In addition, miRNAs have also been suggested to be involved in the CSR; however, a few fundamental questions remain largely unanswered (Cimmino et al 2005;Leung et al 2006;Marsit et al 2006;Kulshreshtha et al 2007;Leung and Sharp 2007;Babar et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNAs associated with hyperthermia-induced cellular stress response

Wilmink

Roth

Ibey

et al. 2010

Cell Stress and Chaperones

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MicroRNAs (miRNAs) are a class of small RNAs that play a critical role in the coordination of fundamental cellular processes. Recent studies suggest that miRNAs participate in the cellular stress response (CSR), but their specific involvement remains unclear. In this study, we identify a group of thermally regulated miRNAs (TRMs) that are associated with the CSR. Using miRNA microarrays, we show that dermal fibroblasts differentially express 123 miRNAs when exposed to hyperthermia. Interestingly, only 27 of these miRNAs are annotated in the current Sanger registry. We validated the expression of the annotated miRNAs using qPCR techniques, and we found that the qPCR and microarray data was in well agreement. Computational target-prediction studies revealed that putative targets for the TRMs are heat shock proteins and Argonaute-2-the core functional unit of RNA silencing. These results indicate that cells express a specific group of miRNAs when exposed to hyperthermia, and these miRNAs may function in the regulation of the CSR. Future studies will be conducted to determine if other cells lines differentially express these miRNAs when exposed to hyperthermia.

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Section: Discussionmentioning

confidence: 99%

Identification of microRNAs associated with hyperthermia-induced cellular stress response

Wilmink

Roth

Ibey

et al. 2010

Cell Stress and Chaperones

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“…Recent studies revealed the involvement of miRNAs in apoptosis signaling (5). For instance, miR-15 and miR-16 have been shown to induce apoptosis by targeting Bcl-2 (6).…”

Section: Micrornas (Mirnas)mentioning

confidence: 99%

MicroRNA-206 Targets notch3, Activates Apoptosis, and Inhibits Tumor Cell Migration and Focus Formation

Song

Zhang

Wang

2009

Journal of Biological Chemistry

191

176

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MicroRNAs contribute to cancer development by acting as oncogenes or tumor suppressor genes. However, only a few microRNA target genes were determined. We identified a nearly perfect complementarity between miR-206 and the 3-untranslated regions of both mouse and human notch3. Expression of miR-206 decreased the luciferase activity dose-dependently when cotransfected with the mouse or human notch3 3-untranslated region-luciferase reporter containing the miR-206 target site in HeLa cells. This suppression was relieved by deletion and mutation of the miR-206-binding site and was partially recovered by expression of notch3 or by a specific inhibitor of miR-206. Interestingly, overexpression of miR-206 decreased the levels of both Notch3 protein and mRNA. Expression of miR-206 markedly induced apoptotic cell death and blocked the anti-apoptotic activity of Notch3. In addition, ectopic expression of miR-206 inhibited HeLa cell migration and focus formation. Therefore, we identified miR-206 as a pro-apoptotic activator of cell death, which was associated with its inhibition of notch3 signaling and tumor formation. The inhibition of cancer cell migration and focus formation by miR-206 strongly suggests that miR-206 may function as a novel tumor suppressor. MicroRNAs (miRNAs)2 regulate gene expression by binding to the 3Ј-untranslated regions (3Ј-UTRs) of specific mRNAs (1) and play important roles in development, proliferation, and differentiation (2-4). Recent studies revealed the involvement of miRNAs in apoptosis signaling (5). For instance, miR-15 and miR-16 have been shown to induce apoptosis by targeting Bcl-2 (6). miR-34a can be regulated by p53, which promotes apoptosis (7,8). Despite the growing evidence for their importance in carcinogenesis (9), limited information is available about their function in human cancers. The future challenges are to identify the biological targets of miRNAs and the signaling pathways they regulate during oncogenesis.Early studies identified miR-206 as a skeletal musclespecific miRNA involved in muscle development (10 -12). Recent studies showed that miR-206 targets the estrogen receptor (13) and is down-regulated in estrogen receptorpositive breast cancer (14). It is thus postulated that miR-206 may be associated with breast cancer metastasis (15). In addition to its high expression in muscle, miR-206 was also reported to be expressed in brain associated with schizophrenia (16) and in brown adipocytes (17). The level of miR-206 is increased in bone marrow-derived DC19ϩ WM cells associated with Waldenström macroglobulinemia (18). Despite a broader tissue-specific expression than originally anticipated, the physiological function of miR-206 in cancer progression remains largely unknown.In this study, we report several novel findings. We identify notch3 (Notch homolog 3) as a novel miR-206 target. We reveal miR-206 as a potent apoptotic cell death inducer via cross-talk with notch3. We further show that miR-206 inhibits tumor cell migration and focus formation. Our study suggests mi...

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“…Cell apoptosis is a complex process that may be achieved through the death-receptor or the mitochondria pathways [55,56]. Most antitumor drugs such as antimetabolites, and alkylating agents inhibit cancer proliferation by promoting cell apoptosis or cell cycle arrest.…”

Section: Mirnas Involved In Chemoresistance Through Cell Apoptosis Rementioning

confidence: 99%

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Rolfo¹,

Fanale²,

Hong³

et al. 2014

CPB

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Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient disruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, intrinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional chemotherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing mRNA degradation or translational repression. Accumulating evidence suggests that impairment of candidate miRNAs may be involved in the acquisition of tumor cell resistance to conventional chemotherapy and novel biological agents by affecting the drug sensitivity of cancer cells. The modulation of these miRNAs, using antagomiRs or miRNA mimics, can restore key gene networks and signaling pathways, and optimize anticancer therapies by inhibition of tumor cell proliferation and increasing the drug sensitivity. Therefore, miRNA-based therapeutics provides an attractive anti-tumor approach for developing new and more effective individualized therapeutic strategies, improving drug efficiency, and for predicting the response to different anticancer drugs. In this review, we present an overview on the role of miRNAs in resistance mechanisms of NSCLC, discussing the main studies on the aberrations in apoptosis, cell cycle and DNA damage repair pathways, as well as in novel drug targets.

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microRNAs and death receptors

Cited by 34 publications

References 114 publications

Identification of microRNAs associated with hyperthermia-induced cellular stress response

Identification of microRNAs associated with hyperthermia-induced cellular stress response

MicroRNA-206 Targets notch3, Activates Apoptosis, and Inhibits Tumor Cell Migration and Focus Formation

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

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