Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro

Han, Xiaosi; Li, Rong; Zhang, Wenbin; Yang, Xiuhua; Wheeler, Crystal G.; Friedman, Gregory K.; Province, Paula; Ding, Qiang; You, Zhiying; Fathallah‐Shaykh, Hassan M.; Gillespie, G. Yancey; Zhao, Xinyang; King, Peter H.; Nabors, L. Burt

doi:10.1007/s11060-014-1419-0

Cited by 85 publications

(83 citation statements)

References 43 publications

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“…PRMT5 knockdown also lead to apoptosis and cell cycle arrest in glioma cells [22]. Moreover, the expression of PRMT5 is correlated with malignant grade in gliomas and plays a pivotal role in the proliferation of glioma cells in vitro [23]. These findings are in line with our results that also revealed a novel mechanism that regulated the expression of PRMT5.…”

Section: Discussionsupporting

confidence: 88%

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma

Cai

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. Methods: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed. The levels of proteins were detected using western blot. Bioinformatics analysis and luciferase reporter assays were applied to the analysis of the relationship between SNHG16, miR-4518 and PRMT5. Cell viability and apoptosis were measured using MTT and apoptosis ELISA assay, respectively. Results: SNHG16 was highly expressed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. Knockdown of SNHG16 inhibits the viability and induces apoptosis of glioma cells. Further investigation revealed that SNHG16 could up-regulate the expression of miR-4518 targeted gene PRMT5 via acting as an endogenous sponge of miR-4518. Moreover, SNHG16 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway. Conclusion: Our study revealed a novel SNHG16-miR-4518-PRMT5 pathway regulatory axis in glioma pathogenesis. SNHG16 could be used as a potential therapeutic target in the treatment of glioma.

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Section: Discussionsupporting

confidence: 88%

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma

Cai

et al. 2018

Cell Physiol Biochem

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“…PRMT5 is a type II PRMT that catalyses the transfer of methyl groups from S-adenosyl methionine to the arginine residues of histones or non-histone proteins and is involved in numerous cellular processes (19,30). Because PRMT5 possesses multiple cellular functions, it is an important determinant of oncological properties of various malignancies (12)(13)(14)17,18). In the present study, analyses of the expression levels of PRMT5 and their effects on the phenotypes of GC cell lines, patient characteristics and outcomes were performed to assess the potential of PRMT5 as a novel biomarker and therapeutic target for patients with GC.…”

Section: Discussionmentioning

confidence: 99%

“…Because PRMT5 is implicated in diverse cellular and biological processes such as transcriptional regulation, RNA metabolism, ribosome biogenesis, Golgi apparatus homeostasis and cell cycle regulation, PRMT5 is generating increased interest in the field of cancer research (12,15,16). For example, PRMT5 is expressed at higher levels compared with normal tissues in leukemias, lymphomas and gliomas as well as in ovarian, breast, prostate and lung cancers (13,14,(17)(18)(19)(20). In contrast, the expression levels of PRMT5 in gastroenterological malignancies and the biological function of PRMT5 remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer

Kanda

Shimizu

Fujii

et al. 2016

International Journal of Oncology

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Abstract. Identification of novel gastric cancer (GC)-related molecules is necessary to improve management of patients with GC in both diagnostic and therapeutic aspects. The aim of the present study was to determine whether protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in the progression of GC and whether it serves as a novel diagnostic marker and therapeutic target. We conducted global expression profiling of GC cell lines and RNA interference experiments to evaluate the effect of PRMT5 expression on the phenotype of GC cells. We analysed tissues of 179 patients with GC to assess the association of PRMT5 mRNA levels with clinicopathological factors. Differential expression of PRMT5 mRNA by GC cell lines correlated positively with the levels of GEMIN2, STAT3 and TGFB3. PRMT5 knockdown reduced the proliferation, invasion and migration of a GC cell line. PRMT5 mRNA levels were significantly higher in GC tissues than the corresponding adjacent normal tissues and were independent of tumour depth, differentiation and lymph node metastasis. High PRMT5 expression was an independent risk factor of positive peritoneal lavage cytology (odds ratio 3.90, P=0.003) and decreased survival. PRMT5 enhances the malignant phenotype of GC cell lines and its expression in gastric tissues may serve as a biomarker for patient stratification and a potential target of therapy.

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“…6,7 PRMT5 expression positively correlates with the grade of malignancy in astrocytomas and inversely correlates with survival. 8,9 In concordance with this role, depletion of PRMT5 in glioma cell lines failed to form tumours in mice engrafted intracranially with GBM xenografts. 8 …”

Section: Introductionmentioning

confidence: 86%

PRMT5–PTEN molecular pathway regulates senescence and self-renewal of primary glioblastoma neurosphere cells

Banasavadi-Siddegowda

Russell

Frair

et al. 2016

Oncogene

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Glioblastoma (GBM) represents the most common and aggressive histologic subtype among malignant astrocytoma and is associated with poor outcomes because of heterogeneous tumour cell population including mature non-stem-like cell and immature stem-like cells within the tumour. Thus, it is critical to find new target-specific therapeutic modalities. Protein arginine methyltransferase enzyme 5 (PRMT5) regulates many cellular processes through its methylation activity and its overexpression in GBM is associated with more aggressive disease. Previously, we have shown that silencing of PRMT5 expression in differentiated GBM cell lines results in apoptosis and reduced tumour growth in mice. Here, we report the critical role of PRMT5 in GBM differentiated cells (GBMDC) grown in serum and GBM neurospheres (GBMNS) grown as neurospheres in vitro. Our results uncover a very significant role for PRMT5 in GBMNS self-renewal capacity and proliferation. PRMT5 knockdown in GBMDC led to apoptosis, knockdown in GBMNS led to G1 cell cycle arrest through upregulation of p27 and hypophoshorylation of retinoblastoma protein, leading to senescence. Comparison of impact of PRMT5 on cellular signalling by the Human Phospho-Kinase Array and chromatin immunoprecipitation-PCR revealed that unlike GBMDC, PRMT5 regulates PTEN expression and controls Akt and ERk activity in GBMNS. In vivo transient depletion of PRMT5 decreased intracranial tumour size and growth rate in mice implanted with both primary tumour-derived GBMNS and GBMDC. This is the first study to identify PTEN as a potential downstream target of PRMT5 and PRMT5 is vital to support both mature and immature GBM tumour cell populations.

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Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro

Cited by 85 publications

References 43 publications

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma

Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer

PRMT5–PTEN molecular pathway regulates senescence and self-renewal of primary glioblastoma neurosphere cells

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