Suppression of tumorigenicity by MicroRNA-138 through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop in glioblastoma multiforme

Qiu, Siqi; Huang, Daquan; Yin, Deling; Li, Fangcheng; Li, Xiangping; Kung, Hsiang‐Fu; Peng, Ying

doi:10.1016/j.bbadis.2013.05.015

Cited by 93 publications

(68 citation statements)

References 53 publications

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“…In addition, multivariate survival analysis indicated that low expression of miR-138 was an independent prognostic factor for patients with hepatocellular carcinoma (31). In glioblastoma, high expression levels of miR-138 were associated with a long overall and progression-free survival time (32). These findings suggested that miR-138 may represent a promising prognostic biomarker of human cancer.…”

Section: Discussionmentioning

confidence: 69%

“…Downregulation of miR-138 has been identified in several cancer types, including breast cancer (21), bladder cancer (22), larynx carcinoma (23), colorectal cancer (24,25), non-small cell lung cancer (26,27), oral squamous cell carcinoma (28), gallbladder carcinoma (29), pancreatic cancer (30), hepatocellular carcinoma (31) and glioblastoma (32). More significantly, miR-138 expression levels were observed to be correlated with clinicopathological features of cancer patients.…”

Section: Discussionmentioning

confidence: 98%

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MicroRNA‑138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9

Wang

Jin

2017

Oncol Lett

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Abstract. An accumulating number of studies have reported that the expression levels of microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types, including renal cell carcinoma (RCC). miRNAs play essential functions in tumorigenesis and the progression of tumors by serving as oncogenes or tumor suppressors. Recently, the expression and functions of miR-138 have been studied in a number of human cancer types; however, its role in RCC remains poorly understood. In the present study, the results revealed that miR-138 was significantly downregulated in RCC cell lines and tissues, and that low expression levels of miR-138 were correlated with histological grade, tumor stage and lymph node metastasis. In functional studies, restoration of miR-138 expression inhibited cell proliferation and invasion of ACHN and A498 cells. In addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9 knockdown inhibited cell proliferation and invasion of RCC, with a similar effect to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the disease. These findings indicate that miR-138 may present a novel target for therapeutic strategies in RCC.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 98%

MicroRNA‑138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9

Wang

Jin

2017

Oncol Lett

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“…miR-138/SP1-based targeted therapy could therefore represent a promising therapeutic strategy for HCC patients. Downregulation of miR-138 has been reported in diverse types of human cancer, including anaplastic thyroid carcinoma (21), head and neck squamous cell carcinoma (22), clear cell renal cell carcinoma (23), ovarian cancer (24), glioblastoma (25), colorectal cancer (26), non-small cell lung cancer (NSCLC) (27), pancreatic cancer (28) and breast cancer (29). Furthermore, reduced miR-138 expression was associated with a number of cancer characteristics.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells

et al. 2017

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Abstract. The identification of microRNAs (miRNAs/miRs) has enabled the improved understanding of the carcinogenesis and progression of hepatocellular carcinoma (HCC). miRNAs are small non-coding RNAs comprised of 19-24 nucleotides that regulate the expression of target genes. In the present study, miR-138 was demonstrated to be downregulated in human HCC tissues and cell lines. Restoration of miR-138 expression repressed the proliferation, migration and invasion of HCC cells. Furthermore, specificity protein 1 (SP1) was identified as a target gene of miR-138 in HCC using bioinformatics analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Knockdown of SP1 produced similar suppressive effects to those induced by miR-138 overexpression in HCC cells. These results indicate that miR-138 targeted SP1 to repress the growth, migration and invasion of HCC cells, and may therefore represent a therapeutic target in human HCC.

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“…partial From the therapeutic point of view, EZH 2-mediated signal loop, EZH2-CDK4/6-pRb-E2F1, which is involved in carcinogenesis of glioma, could be inhibited by the candidate miRNA. MiR-138 is the miRNA that is diminished in gB samples and potent to suppress EZH2 expression through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop (32).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of aldh1, ezh2 and ki-67 in astrocytic gliomas

Ahmed

Rashed²,

Hegazy³

et al. 2016

TJPATH

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Objective: tumor stem cells have been found in a variety of neoplasms and stated to have a role in tumor progression. This study aimed to evaluate the prognostic significance of biomarkers which are said to be related to these cells, i.e., EZH2, ALDH1 and Ki-67, and their correlation with each other in astrocytic gliomas. Material and Method:Formalin-fixed, paraffin-embedded tissue specimens of 40 patients with astrocytic glioma who underwent initial surgery during the period from December 2011 to May 2014 at Zagazig University Hospitals were enrolled in the study. Consecutive 4-μm thick sections from formalin-fixed, paraffin-embedded tissue blocks were prepared and stained with hematoxylin and eosin for histopathological evaluation. immunohistochemical analysis using ALDH1, EZH2 and Ki-67 antibodies were performed to examine the cases.Results: A total of forty patients; 22 males and 18 females were studied. The lesions were classified as follows: 14 cases of low-grade astrocytoma (WHO grade i or ii), 11 cases of anaplastic astrocytoma (WHO grade iii), and 15 glioblastomas (WHO grade iV). There was a significant increase in ALDH1 immunoreactivity with increasing the grade of astrocytoma (mean ±SD = 0.2 ±0.4, 0.5 ±0.6, 1.1 ±1.3 and 2.95 ±2.97 in grade i to iV astrocytic gliomas, respectively). This expression was significantly correlated with overall survival (OS) and progression-free survival (pFS) (p=0.004). EZH2 expression was also significantly associated with advanced grades (mean ±SD =1.35 ±0.4, 3.1 ±2.6, 7.2 ±3.5 and 9.9 ±4.1, in grade i to iV astrocytic gliomas, respectively). EZH2 and Ki-67 expressions were found to be correlated with OS and pFS (p < 0.001).Conclusion: increased expression of ALDH1, EZH2 and Ki67 are found to be associated with unfavourable prognosis in patients with astrocytic gliomas and may predict therapeutic modalities.

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Suppression of tumorigenicity by MicroRNA-138 through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop in glioblastoma multiforme

Cited by 93 publications

References 53 publications

MicroRNA‑138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9

MicroRNA‑138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9

MicroRNA‑138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells

Prognostic value of aldh1, ezh2 and ki-67 in astrocytic gliomas

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