P53-induced microRNA-107 inhibits proliferation of glioma cells and down-regulates the expression of CDK6 and Notch-2

Chen, Lei; Zhang, Run; Li, Peng; Liu, Yi; Qin, Kun; Fa, Zhiqiang; Liu, Yijing; Ke, Yiquan; Jiang, Xiao-dan

doi:10.1016/j.neulet.2012.11.047

Cited by 62 publications

(65 citation statements)

References 32 publications

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“…Therefore, restoring the function of wild-type p53 in p53-inactivated tumor cells is a potential treatment for certain types of tumor. In recent years, adenovirus-mediated p53 gene therapy has been rapidly developed as a promising antitumor strategy and has been employed in a number of preclinical experiments and clinical studies (22,25,26). In this regard, p53 is a common gene inserted in CRAd to control tumor cell growth and to cause cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Chen et al (26) demonstrated that p53-induced microRNA-107 inhibited brain tumor cell growth, which indicates that it serves as a tumor suppressor and thus, may be used as a target for glioma therapy. Additionally, Yang et al (27) suggested a combination of recombinant adenovirus-p53 (rAd-p53) with fractionated stereotactic radiotherapy (fSRT) is an effective and relatively safe method for the treatment of primary hepatocellular carcinoma (HCC) compared with fSRT monotherapy, indicating that rAd-p53 combined with fSRT may be preferred as a local method to treat primary HCC if the patients are unable to undergo surgery or refuse operation.…”

Section: Discussionmentioning

confidence: 99%

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A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

Liu

Yang

et al. 2017

Oncol Lett

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Abstract. Gliomas are the most common type of primary brain tumor in adults, where more than half of the cases are malignant, and the prognosis is poor. The early viral 1A (E1A) protein has been widely recognized to be essential for adenoviral replication and production of progeny virions in human cells, a process that is regulated by human telomerase reverse transcriptase. The p53 gene, as a tumor suppressor, regulates diverse cellular processes, including cell cycle arrest, cell autophagy, senescence and apoptosis. Dysfunction of the p53 pathways is common in malignant gliomas. Exogenous expression of p53 during adenovirus replication in human cancer cells may accelerate cell death and improve the release of early virus progeny. In the present study, a conditionally replicative adenovirus (CRAd) Ad-Tp-E1A-Gp-p53, which expressed functional p53 protein when replicating in cancer cells, was constructed. Next, the level of p53 expression in U251 cells was determined by western blot analysis, and the inhibitory effect of Ad-Tp-E1A-Gp-p53 on U251 cells was detected via an MTT assay. The results indicated that p53 expression was upregulated with an increase in the multiplicity of infection (MOI) of Ad-Tp-E1A-Gp-p53. Additionally, the inhibitory effects of Ad-Tp-E1A-Gp-p53 in different groups were significantly different (P<0.05), with the inhibition ratio of the experimental groups being higher, compared with the control group (P<0.05). Furthermore, the inhibition ratio increased with increases in the MOI of Ad-Tp-E1A-Gp-p53. Therefore, the expression of functional p53 and that of E1A may increase the potency of CRAd, and overexpression of p53 through CRAd is a promising approach to more effective treatments in a number of human cancer types.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

Liu

Yang

et al. 2017

Oncol Lett

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“…Regarding the function of miR-107 in cancer, reduced miR-107 expression has been reported in various types of cancer [69][70][71][72][73][74][75][76][77][78] , and several recent studies have identified the tumor suppressor functions of miR-107. One crucial function of miR-107 that has been identified is the inhibition of oncogenes, such as CDK8 in breast cancer 71 , the ATR/Chk1 pathway in cervical cancer 79 , HIF-1, CCND1, and NFKB1 in colon cancer 80,81 , CDK in gastric cancer 70 , CDK6, Notch-2, and VEGF in glioma Expression profiles of miR-107 in human organs.…”

Section: Discussionmentioning

confidence: 99%

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Imamura

Komatsu

Ichikawa

et al. 2017

Journal of the American College of Surgeons

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This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small-and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (P < 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCa patients (P = 0.0424; hazard ratio, 2.95). miR-107 overexpression in PCa cells induced G1/S arrest with the production of p21 and inhibited cell proliferation through the transcriptional regulation of Notch2. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. Depletion of the tumor suppressor miR-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCa.Pancreatic cancer (PCa) is the fourth leading cause of cancer-related death in Japan and the United States 1 and the seventh worldwide 2 . PCa is one of the most aggressive cancer types and constitutes a global health problem, with more than 330,000 cancer-related deaths annually 2 . Although perioperative chemo-and/or radiotherapy regimens, surgical techniques and perioperative management have greatly progressed, PCa continues to present an extremely poor prognosis. Even now, the median survival time of PCa patients is 5 to 8 months, and their 5-year survival rate is less than 10%. This is because PCa develops with no symptoms, local invasiveness, or metastases to distant organs in the early stage of its clinical course [3][4][5] . Therefore, novel early diagnostic tools and effective treatment strategies are urgently needed to improve the survival rate of PCa patients.Because understanding the molecular mechanisms of tumorigenesis and identifying clinical biomarkers and molecular targets for PCa contribute to improving the management of this lethal disease, several studies have attempted to detect the biological factors involved in the malignant potential of PCa 6, 7 . Nevertheless, in clinical settings, no molecule has been used as an early diagnostic biomarker, and only a few molecules have been

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“…46 Blockage of CDK6 expression by microRNAs (miRNAs) has been shown to inhibit the proliferation of gliomas, medulloblastoma, prostate, bladder, gastric, hepatocellular, and lung cancer cells, indicating the significant role of CDK6 in the initiation and progression of these cancers. [51][52][53][54][55][56][57][58] These observations, coupled with the fact that mice lacking D-type cyclins and/or CDK4/6 are viable, make targeting components of the CDK4/6 cyclin D-INK4-pRb-E2F pathway a highly attractive anti-cancer strategy. 12,14 CDK6 and hematological malignancies Acute myeloid leukemia (AML) is a malignant transformation of hematopoietic cells characterized by an increase in the number of myeloid cells in the marrow and an arrest in their maturation.…”

Section: Introductionmentioning

confidence: 99%

Targeting CDK6 in cancer: State of the art and new insights

et al. 2015

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Cyclin-dependent kinase 6 (CDK6) plays a vital role in regulating the progression of the cell cycle. More recently, CDK6 has also been shown to have a transcriptional role in tumor angiogenesis. Up-regulated CDK6 activity is associated with the development of several types of cancers. While CDK6 is over-expressed in cancer cells, it has a low detectable level in non-cancerous cells and CDK6-null mice develop normally, suggesting a specific oncogenic role of CDK6, and that its inhibition may represent an ideal mechanism-based and low toxic therapeutic strategy in cancer treatment. Identification of selective small molecule inhibitors of CDK6 is thus needed for drug development. Herein, we review the latest understandings of the biological regulation and oncogenic roles of CDK6. The potential clinical relevance of CDK6 inhibition, the progress in the development of small-molecule CDK6 inhibitors and the rational design of potential selective CDK6 inhibitors are also discussed.

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P53-induced microRNA-107 inhibits proliferation of glioma cells and down-regulates the expression of CDK6 and Notch-2

Cited by 62 publications

References 32 publications

A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Targeting CDK6 in cancer: State of the art and new insights

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