MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme

Li, Yiming; Li, Weiqing; Yang, Yue; Lu, Yao; He, Cheng; Hu, Guohan; Liu, Huimin; Chen, Juxiang; He, Jia; Yu, Hongyu

doi:10.1016/j.brainres.2009.06.053

Cited by 193 publications

(125 citation statements)

References 27 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…For example, miR-21 is overexpressed in glioblastoma and mediates chemoresistance to the chemotherapeutic agent VM-26 in glioblastoma cells (32). The tumor necrosis factor-related apoptosis-inducing ligand in combination with miR-21 suppression leads to a synergistic increase in caspase activity and a decrease in cell viability in human glioma cells (33).…”

Section: Foxo3a Targeting Mir-21mentioning

confidence: 99%

Foxo3a Regulates Apoptosis by Negatively Targeting miR-21

Wang

2010

Journal of Biological Chemistry

100

View full text Add to dashboard Cite

MicroRNAs are a class of small non-coding RNAs and participate in the regulation of apoptotic program. Although miR-21 is able to inhibit apoptosis, its expression regulation and downstream targets remain to be fully elucidated. Here we report that the transcriptional factor Foxo3a initiates apoptosis by transcriptionally repressing miR-21 expression. Our results showed that doxorubicin could simultaneously induce the translocation of Foxo3a to the cell nuclei and a reduction in miR-21 expression. Knockdown of Foxo3a resulted in an elevation in miR-21 levels, whereas enforced expression of Foxo3a led to a decrease in miR-21 expression. In exploring the molecular mechanism by which Foxo3a regulates miR-21, we observed that Foxo3a bound to the promoter region of miR-21 and suppressed its promoter activity. These results indicate that Foxo3a can transcriptionally repress miR-21 expression. In searching for the downstream targets of miR-21 in apoptosis, we found that miR-21 suppressed the translation of Fas ligand (FasL), a pro-apoptotic factor. Furthermore, Foxo3a was able to up-regulate FasL expression through down-regulating miR-21. Our data suggest that Foxo3a negatively regulates miR-21 in initiating apoptosis. miRNAs 2 are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Recently, the work on miRNAs renovates our understanding about apoptotic regulation. They can be classified as either pro-or anti-apoptotic miRNAs (1, 2). For example, miR-1 participates in the initiation of apoptosis (3), whereas miR-21 is able to inhibit apoptosis (4). miRNAs are expressed at a constant level under physiological condition, and their functions depend on their expression levels. It remains a challenging question as to how their expression is regulated in the apoptotic program.The forkhead family of transcription factors is characterized by the presence of a conserved 100-amino acid DNA binding domain and participate in regulating diverse cellular functions such as apoptosis, differentiation, metabolism, proliferation, and survival (5). Foxo3a is a substrate of protein kinase Akt, and its transcriptional output is controlled via phosphorylation. In the absence of cellular stimulation and when Akt is inactive, Foxo3a is localized within the nucleus where it performs transcription of target genes. However, upon phosphorylation by Akt at Thr-32, Ser-253, and Ser-315, it binds to 14-3-3 and cannot exert the transcriptional function (6).Fas ligand (FasL) is a potential transcriptional target of Foxo3a, but the transcriptional output can be either activation or suppression. It has been reported that Foxo3a can stimulate FasL expression, thereby triggering apoptosis (6). However, there is also evidence showing that Foxo3a decreases the expression of FasL (7). The molecular mechanism by which Foxo3a regulates FasL expression remains further elusive. miR-21 has been shown to regulate apoptosis by targeting a variety of apoptotic factors. It contributes to glioma malignancy by down-regulating matrix meta...

show abstract

Section: Foxo3a Targeting Mir-21mentioning

confidence: 99%

Foxo3a Regulates Apoptosis by Negatively Targeting miR-21

Wang

2010

Journal of Biological Chemistry

100

View full text Add to dashboard Cite

show abstract

“…Loss of PDCD4 expression is closely associated with the progression of a number of tumors, including glioblastomas (7), and kidney, ovarian and lung cancer (8)(9)(10). Low PDCD4 expression levels correlate with poor outcomes in patients with glioblastoma multiforme (11).…”

Section: Introductionmentioning

confidence: 99%

Suppression of PDCD4 mediated by the long non-coding RNA HOTAIR inhibits the proliferation and invasion of glioma cells

Chen¹,

Bian²,

Zhao³

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Programmed cell death protein 4 (PDCD4) has recently been demonstrated to be implicated in translation and transcription, and the regulation of cell growth. However, the mechanisms underlying PDCD4 function in glioma cells remain to be elucidated. The current study investigated the function and regulation of PDCD4 and the results demonstrated that the expression of PDCD4 was significantly reduced in glioma cells compared with normal cells. When PDCD4 was overexpressed in glioma cells, the proliferation rate and invasive capability of the cells greatly decreased, suggesting that PDCD4 functions as a tumor suppressor in this cell type. In addition, the histone modification status of the PDCD4 gene was analyzed, and chromatin immunoprecipitation assay identified a high density of histone 3 lysine 27 trimethylation on the promoter of PDCD4, which was associated with the long non-coding RNA, homeobox transcript antisense RNA (HOTAIR). The expression of HOTAIR was significantly increased in glioma cells compared with normal cells, and it exerted its function in a polycomb repressive complex 2-dependent manner. These results may provide novel approaches to therapeutically target PDCD4 and HOTAIR in patients with gliomas. IntroductionHuman gliomas are the most prevalent malignant neoplasms of the central nervous system, with an annual incidence of ~5/100,000 worldwide (1). Despite the use of aggressive surgery in combination with chemotherapy, biological therapy and radiotherapy, gliomas continue to be therapeutically challenging (2). For patients with glioblastoma, the relative 5-year survival rate is <5% (3). Novel therapies for the treatment of glioma are warranted; recent advances in the understanding of the molecular and biological nature of this disease may facilitate the development of successful therapeutics (4).PDCD4 protein was initially determined to be overexpressed during apoptosis, which subsequently suppresses tumorigenesis (5,6). Loss of PDCD4 expression is closely associated with the progression of a number of tumors, including glioblastomas (7), and kidney, ovarian and lung cancer (8-10). Low PDCD4 expression levels correlate with poor outcomes in patients with glioblastoma multiforme (11). The frequent loss of PDCD4 in glioblastoma multiforme is partly due to epigenetic silencing secondary to 5' cytosine-phosphate-guanine island methylation (12), in addition to overexpression of microRNA (miRNA)-21, which targets PDCD4 mRNA for degradation (13). Although several studies have examined PDCD4 in glioma, the detailed molecular mechanisms underlying the role of PDCD4 in glioma remain poorly understood.Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides, which are involved in various important events, including transcriptional, epigenetic and post-transcriptional regulation (14,15). A previous study profiled the lncRNA homeobox transcript antisense RNA (HOTAIR), and the results demonstrated that HOTAIR was closely correlated with poor prognosis, molecular ...

show abstract

“…In addition to PDCD4 and PTEN, miR‐21 also exerts its prooncogenic effect by downregulating numerous targets including ANP32A, SMARCA4, SPRY2, IGFBP3, LRRFIP1, and RECK . Through these targets, miR‐21 can influence numerous biological processes in addition to the promotion of cell cycle progression, including promotion of invasion and metastasis and resistance to chemotherapeutics 37, 38, 39, 40, 41, 42, 43, 44. Notably, inhibition of miR‐21 expression can repress tumor growth 37, 43, 45.…”

Section: Introductionmentioning

confidence: 99%

“…89 determined that overexpression of miR‐21 significantly inhibited the effect of TMZ on apoptosis, which was mediated through downregulation of proapoptotic proteins Bax and caspase‐3 as well as upregulation of antiapoptotic protein Bcl‐2. Moreover, numerous other studies have investigated the impact of miR‐21 on drug resistance in GBM, finding that inhibiting miR‐21 can enhance the chemosensitivity of human GBM cells to TMZ, paclitaxel, sunitinib, doxorubicin, and VM‐26 39, 90, 91, 92, 93, 94.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

Harish²,

et al. 2016

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA‐based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA‐based therapies could provide a critical step forward in cancer treatment.

show abstract

MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme

Cited by 193 publications

References 27 publications

Foxo3a Regulates Apoptosis by Negatively Targeting miR-21

Foxo3a Regulates Apoptosis by Negatively Targeting miR-21

Suppression of PDCD4 mediated by the long non-coding RNA HOTAIR inhibits the proliferation and invasion of glioma cells

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

Contact Info

Product

Resources

About