Downregulation of miR-544 in tissue, but not in serum, is a novel biomarker of malignant transformation in glioma
20
Citation
29
Reference
10
Related Paper
Citation Trend
Abstract:
Low-grade glioma is predisposed to progress to anaplastic astrocytoma and eventually secondary glioblastoma. The malignant transformation may involve the accumulation of multiple genetic alterations. The purpose of this study was to explore the role of miR-544 in glioma progression and discuss whether it may be a novel biomarker of malignant transformation. The expression of miR-544 was measured in a series of 198 glioma samples (63 low-grade glioma, 44 anaplastic astrocytoma and 91 glioblastoma tumors) using microarrays. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the expression levels of miR-544 in tissue and serum samples in an independent validated cohort (25 low-grade glioma, 21 anaplastic astrocytoma and 20 glioblastoma tumors). A Pearson correlation analysis was performed to examine the correlation between miR-544 levels of tissue and serum samples. Microarrays revealed that the expression levels of miR-544 decreased significantly in anaplastic gliomas (P<0.01) or glioblastoma (P<0.01) compared with low-grade gliomas. In an independent cohort of glioma patients, miR-544 exhibited a progression-associated downregulation in glioma tumors. The levels of miR-544 in serum samples tended to be lower in anaplastic and glioblastoma patients compared with low-grade gliomas, but with no significant difference. The Pearson correlation analysis revealed a weakly positive correlation between tissue and serum levels of miR-544. These data support a significant role for miR-544 aberration in the malignant transformation of glioma. The downregulation of miR-544 in tissue may be used as a novel biomarker.Keywords:
Anaplastic astrocytoma
Tissue microarray
Malignant Transformation
The aim of the present study was to examine the expression of phosphoglycerate mutase 1 (PGAM1) in astrocytomas, and to investigate its role in the progression of astrocytomas. The expression of PGAM1 mRNA in rat C6 glioma cells and normal astrocytes was determined using the reverse transcription‑semi‑quantitative polymerase chain reaction, and immunohistochemistry was used to detect the expression of PGAM1 protein in human astrocytomas and adjacent brain tissue. These data suggested that the expression of PGAM1 in rat C6 glioma cells was significantly increased compared with that of normal astrocytes (P<0.05), and the expression of PGAM1 protein in human astrocytoma tissue was significantly increased compared with that of the brain tissue surrounding the tumor (P<0.05). In addition, PGAM1 protein was more frequently expressed in high‑grade astrocytomas compared with low‑grade astrocytomas. These data indicate that the expression of PGAM1 is increased in C6 cells and human astrocytomas, and PGAM1 is probably involved in the tumorigenesis and progression of glioma, which may be a potential target for glioma treatment.
Anaplastic astrocytoma
Cite
Citations (14)
Tumor progression
Cite
Citations (29)
Tissue microarray
Anaplastic astrocytoma
Cite
Citations (20)
MicroRNA (miR)‑27b has been reported to participate in glioma. However, a detailed role of miR‑27b and the underlying mechanism remain largely unknown. The present study found that the expression of miR‑27b was significantly increased in glioma tissues compared with normal adjacent tissues. In addition, miR‑27b was also upregulated in the U87, U251 and SHG44 glioma cell lines compared with normal human astrocytes. Sprouty homolog 2 (Spry2), which has been reported to be associated with invasive glioma, was identified as a novel target of miR‑27b in U251 glioma cells, and the protein expression of Spry2 was negatively regulated by miR‑27b in U251 cells. Additionally, inhibition of miR‑27b and upregulation of Spry2 suppressed glioma cell invasion, while downregulation of Spry2 reversed the suppressive effect of miR‑27b inhibition on glioma cell invasion. These data suggest that miR‑27b may promote glioma cell invasion through direct inhibition of Spry2 expression. The data also suggest that miR‑27b may become a promising molecular target for inhibiting the invasion and metastasis of glioma.
Cite
Citations (23)
Glioma is the most common and aggressive type of primary brain tumor. MicroRNA (miR)-130b functions as a tumor-associated miR. The dysregulation of miR-130b is involved in numerous biological characteristics and properties of certain types of cancer. The present study revealed the function and possible molecular mechanism of miR-130b in glioma cells, reporting that the level of miR-130b was markedly higher, increasing progressively as the histologic grade of the glioma increased, compared with the level in normal tissues. Additionally, the present study demonstrated that patients with high miR-130b expression exhibited a poor 3-year survival rate and miR-130b was an independent factor for predicting the prognosis of patients with glioma. The downregulation of miR-130b reduced invasion and migration in U373 and U87 cells. Furthermore, the downregulation of miR-130b increased peroxisome proliferator-activated receptor-γ (PPARγ) expression and inhibited epithelial-mesenchymal transition (EMT) in glioma cells. The present study identified PPARγ as a direct target of miR-130b in glioma in vitro. Furthermore, PPARγ knockdown was revealed to reduce the effect on EMT caused by the downregulation of miR-130b in U87 cells. The present study demonstrated that miR-130b promotes glioma proliferation, migration and invasion by suppressing PPARγ and subsequently inducing EMT.
Cite
Citations (10)
The prognosis of patients with malignant glioma is always quite poor, and this poor prognosis is probably due to our incomplete understanding of the molecular mechanisms underlying malignant glioma. It is known that myocyte enhancer factor-2D (MEF2D) plays an oncogenic role in hepatocellular carcinoma and promotes the survival of various types of cells. However, little is known about the expression profile and function of MEF2D in malignant glioma. In this study, we investigated the function and expression of MEF2D in malignant glioma. We found that in malignant glioma, there is an aberrantly high expression of MEF2D, which leads to poor prognosis of malignant glioma. The downregulation of MEF2D suppresses the proliferation of malignant glioma cell lines by inducing delay of S and G2/M phases of cell cycle and promoting apoptosis. Furthermore, the overexpression of MEF2D in astrocytes accelerates cell proliferation by regulating cell cycle progression. Furthermore, a mouse malignant glioma model demonstrated that MEF2D deficiency blocks malignant glioma formation in vivo. We conclude that MEF2D may act as a potential oncogene in malignant glioma and thus serve as a candidate target for malignant glioma therapy.
Malignant Transformation
Cite
Citations (7)
Cite
Citations (16)
Long non-coding RNAs (lncRNAs) have been reported to be involved in gene dysregulation in numerous different types of cancer, and have subsequently emerged as a major series of regulatory molecules that participate in a broad range of biological and pathological processes. However, the correlation between the expression levels of lncRNAs and their clinical significance in gastric cancer remains unclear. The aim of the present study was to investigate the potential correlation between lncRNA RP11‑119F7.4 expression and clinicopathological characteristics in gastric cancer, and to identify whether it can serve as a potential diagnostic biomarker of the disease. Total RNA was extracted from the tissues of 96 patients with gastric cancer, in addition to matched non‑tumor adjacent tissues (NATs). Following reverse transcription, lncRNA RP11‑119F7.4 expression levels were determined by quantitative polymerase chain reaction and the association with patient clinicopathological characteristics was further analyzed. A receiver operating characteristic (ROC) curve was constructed to determine the diagnostic value of RP11‑119F7.4. The results demonstrated that RP11‑119F7.4 expression was significantly downregulated in the gastric cancer tissues compared with the matched NATs (P<0.001) and was significantly associated with the macroscopic type (P=0.041) and Lauren grade (P=0.020). The area under the ROC curve was 0.637 (P<0.001). However, no statistically significant differences were observed between RP11‑119F7.4 expression and patient survival. The results of the present study indicate that lncRNA RP11‑119F7.4 may be involved in carcinogenesis and may prove useful as a biomarker for diagnosis and prognostic significance in patients with gastric cancer.
Clinical Significance
Cite
Citations (35)
Drug resistance and disease relapse are still challenging problems in the chemotherapy of colorectal cancer (CRC). Programmed cell death factor 4 (PDCD4) has previously been reported to act as a tumor suppressor and was implicated in the chemosensitivity of numerous types of human malignancy. In this study, the effect of PDCD4 in the sensitivity of CRC to the chemotherapy drug Taxol was investigated. The results confirmed that lower PDCD4 expression was present in CRC tumor tissues, when compared with in normal adjacent tissues (p) and closely associated with the prognosis of patients with CRC. Upregulation of PDCD4 significantly enhanced the sensitivity of CRC cells to Taxol, by partially contributing to pro-apoptosis and anti-invasion pathways, both through upregulation of the apoptosis-associated protein Bax, and downregulation of the anti-apoptosis protein Bcl-2 and invasion-associated proteins MMP-9. These findings might present a novel strategy for sensitizing tumor cells to apoptosis and, thus, overcoming chemotherapy resistance in CRC.
Cite
Citations (10)
Low-grade glioma is predisposed to progress to anaplastic astrocytoma and eventually secondary glioblastoma. The malignant transformation may involve the accumulation of multiple genetic alterations. The purpose of this study was to explore the role of miR-544 in glioma progression and discuss whether it may be a novel biomarker of malignant transformation. The expression of miR-544 was measured in a series of 198 glioma samples (63 low-grade glioma, 44 anaplastic astrocytoma and 91 glioblastoma tumors) using microarrays. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the expression levels of miR-544 in tissue and serum samples in an independent validated cohort (25 low-grade glioma, 21 anaplastic astrocytoma and 20 glioblastoma tumors). A Pearson correlation analysis was performed to examine the correlation between miR-544 levels of tissue and serum samples. Microarrays revealed that the expression levels of miR-544 decreased significantly in anaplastic gliomas (P<0.01) or glioblastoma (P<0.01) compared with low-grade gliomas. In an independent cohort of glioma patients, miR-544 exhibited a progression-associated downregulation in glioma tumors. The levels of miR-544 in serum samples tended to be lower in anaplastic and glioblastoma patients compared with low-grade gliomas, but with no significant difference. The Pearson correlation analysis revealed a weakly positive correlation between tissue and serum levels of miR-544. These data support a significant role for miR-544 aberration in the malignant transformation of glioma. The downregulation of miR-544 in tissue may be used as a novel biomarker.
Anaplastic astrocytoma
Tissue microarray
Malignant Transformation
Cite
Citations (20)