Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Bielli, Pamela; Pagliarini, Vittoria; Pieraccioli, Marco; Caggiano, Cinzia; Sette, Claudio

doi:10.3390/cells9010010

Cited by 22 publications

(18 citation statements)

References 147 publications

(199 reference statements)

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“…As such, their targeting in IBD patients may help to prevent neoplastic transformation. In particular, an oncogenic role associated with regulation of cell cycle proteins [40][41][42] as well as with facilitating splicing of genes retaining introns [43] has been attributed to PRMT5. Unlike other PRMTs, PRMT2 has been rather shown to prevent cancer cell proliferation [44].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Krzystek−Korpacka

Fleszar

Bednarz−Misa

et al. 2020

IJMS

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L-arginine/nitric oxide pathway in Crohn's disease (CD) and ulcerative colitis (UC) is poorly investigated. The aim of current study is to quantify pathway serum metabolites in 52 CD (40 active), 48 UC (33 active), and 18 irritable bowel syndrome patients and 40 controls using mass spectrometry and at determining mRNA expression of pathway-associated enzymes in 91 bowel samples. Arginine and symmetric dimethylarginine decreased (p < 0.05) in active-CD (129 and 0.437 µM) compared to controls (157 and 0.494 µM) and active-UC (164 and 0.52 µM). Citrulline and dimethylamine increased (p < 0.05) in active-CD (68.7 and 70.9 µM) and active-UC (65.9 and 73.9 µM) compared to controls (42.7 and 50.4 µM). Compared to normal, CD-inflamed small bowel had downregulated (p < 0.05) arginase-2 by 2.4-fold and upregulated dimethylarginine dimethylaminohydrolase (DDAH)-2 (1.5-fold) and arginine N-methyltransferase (PRMT)-2 (1.6-fold). Quiescent-CD small bowel had upregulated (p < 0.05) arginase-2 (1.8-fold), DDAH1 (2.9-fold), DDAH2 (1.5-fold), PRMT1 (1.5-fold), PRMT2 (1.7-fold), and PRMT5 (1.4-fold). Pathway enzymes were upregulated in CD-inflamed/quiescent and UC-inflamed colon as compared to normal. Compared to inflamed, quiescent CD-colon had upregulated DDAH1 (5.7-fold) and ornithine decarboxylase (1.6-fold). Concluding, the pathway is deregulated in CD and UC, also in quiescent bowel, reflecting inflammation severity and angiogenic potential. Functional analysis of PRMTs and DDAHs as potential targets for therapy is warranted.

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Section: Discussionmentioning

confidence: 99%

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Krzystek−Korpacka

Fleszar

Bednarz−Misa

et al. 2020

IJMS

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“…Since non-tumor cells express low levels of PRMT5, specific inhibitors of PRMT5 activity that have been developed may show limited cytotoxicity and high specificity against cancer cells, which may facilitate their use of single drug or combination therapy in new cancer treatment methods that are not responsive to conventional therapy (Bielli et al, 2019).…”

Section: Application Of Prmt5 For Multiple Cancersmentioning

confidence: 99%

Protein Arginine Methyltransferase 5 Functions via Interacting Proteins

Liang

Wen

Jiang

et al. 2021

Front. Cell Dev. Biol.

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The protein arginine methyltransferases (PRMTs) are involved in such biological processes as transcription regulation, DNA repair, RNA splicing, and signal transduction, etc. In this study, we mainly focused on PRMT5, a member of the type II PRMTs, which functions mainly alongside other interacting proteins. PRMT5 has been shown to be overexpressed in a wide variety of cancers and other diseases, and is involved in the regulation of Epstein-Barr virus infection, viral carcinogenesis, spliceosome, hepatitis B, cell cycles, and various signaling pathways. We analyzed the regulatory roles of PRMT5 and interacting proteins in various biological processes above-mentioned, to elucidate for the first time the interaction between PRMT5 and its interacting proteins. This systemic analysis will enrich the biological theory and contribute to the development of novel therapies.

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“…The involvement of snRNAs in splicing was thoroughly described earlier [ 122 , 123 ]. The normal functioning of all components of the splicing machinery is critical for many biological processes: so, it is not surprising that splicing disruption is observed in multiple diseases, including glioblastoma [ 124 ].…”

Section: Small Non-coding Rnasmentioning

confidence: 99%

The Role of Non-coding RNAs in the Pathogenesis of Glial Tumors

et al. 2021

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Among the many malignant neoplasms, glioblastoma (GBM) leads to one of the worst prognosis for patients and has an almost 100% recurrence rate. The only chemotherapeutic drug that is widely used for treating glioblastoma is temozolomide, a DNA alkylating agent. Its impact, however, is only minor; it increases patients survival just by 12 to 14 months. Multiple highly selective compounds that affect specific proteins and have performed well in other types of cancer have proved ineffective against glioblastoma. Hence, there is an urgent need for novel methods that could help achieve the long-awaited progress in glioblastoma treatment. One of the potentially promising approaches is the targeting of non-coding RNAs (ncRNAs). These molecules are characterized by extremely high multifunctionality and often act as integrators by coordinating multiple key signaling pathways within the cell. Thus, the impact on ncRNAs has the potential to lead to a broader and stronger impact on cells, as opposed to the more focused action of inhibitors targeting specific proteins. In this review, we summarize the functions of long noncoding RNAs, circular RNAs, as well as microRNAs, PIWI-interacting RNAs, small nuclear and small nucleolar RNAs. We provide a classification of these transcripts and describe their role in various signaling pathways and physiological processes. We also provide examples of oncogenic and tumor suppressor ncRNAs belonging to each of these classes in the context of their involvement in the pathogenesis of gliomas and glioblastomas. In conclusion, we considered the potential use of ncRNAs as diagnostic markers and therapeutic targets for the treatment of glioblastoma.

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Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Cited by 22 publications

References 147 publications

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Protein Arginine Methyltransferase 5 Functions via Interacting Proteins

The Role of Non-coding RNAs in the Pathogenesis of Glial Tumors

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