Genome-Wide Study of Hypomethylated and Induced Genes in Patients with Liver Cancer Unravels Novel Anticancer Targets

Stefańska, Barbara; Cheishvili, David; Suderman, Matthew; Arakelian, Ani; Huang, Jian; Hallett, Michael; Han, Ze‐Guang; Al‐Mahtab, Mamun; Akbar, Sheikh Mohammad Fazle; Khan, Wasif Ali; Raqib, Rubhana; Tanvir, Imrana; Khan, Haseeb Ahmed; Rabbani, Shafaat A.; Szyf, Moshe

doi:10.1158/1078-0432.ccr-13-0283

Cited by 92 publications

(85 citation statements)

References 44 publications

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“…RNMT2 is associated with several human diseases, as it is one of the several genes deleted in the Williams–Beuren neurodevelopmental syndrome [77,78]. It was also reported as a tumoral marker for invasive breast cancer, myeloma cells and hepatocarcinoma [79,80,81], and it might be involved in lung pathologies [82]. …”

Section: Eukaryotic Trm112 Networkmentioning

confidence: 99%

Trm112, a Protein Activator of Methyltransferases Modifying Actors of the Eukaryotic Translational Apparatus

et al. 2017

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Post-transcriptional and post-translational modifications are very important for the control and optimal efficiency of messenger RNA (mRNA) translation. Among these, methylation is the most widespread modification, as it is found in all domains of life. These methyl groups can be grafted either on nucleic acids (transfer RNA (tRNA), ribosomal RNA (rRNA), mRNA, etc.) or on protein translation factors. This review focuses on Trm112, a small protein interacting with and activating at least four different eukaryotic methyltransferase (MTase) enzymes modifying factors involved in translation. The Trm112-Trm9 and Trm112-Trm11 complexes modify tRNAs, while the Trm112-Mtq2 complex targets translation termination factor eRF1, which is a tRNA mimic. The last complex formed between Trm112 and Bud23 proteins modifies 18S rRNA and participates in the 40S biogenesis pathway. In this review, we present the functions of these eukaryotic Trm112-MTase complexes, the molecular bases responsible for complex formation and substrate recognition, as well as their implications in human diseases. Moreover, as Trm112 orthologs are found in bacterial and archaeal genomes, the conservation of this Trm112 network beyond eukaryotic organisms is also discussed.

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Section: Eukaryotic Trm112 Networkmentioning

confidence: 99%

Trm112, a Protein Activator of Methyltransferases Modifying Actors of the Eukaryotic Translational Apparatus

et al. 2017

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“…RASAL2 expression is suppressed by hypermethylation of its promoter, which leads to Ras signaling, and subsequent tumor growth and metastasis in human breast cancer (12,13). Decreased RASAL2 expression is correlated with metastasis, recurrence and poor disease outcome in luminal B tumors (14).…”

Section: Introductionmentioning

confidence: 99%

“…Inactivation of RASAL2 promotes lung cancer metastasis through the induction of EMT via mitogen-activated protein kinase 1 (ERK) activation (16). RASAL2 was reported to be hypomethylated in hepatocellular carcinoma, suggesting that it functions as an oncogene in this cancer (12). However, to the best of our knowledge, no research focusing on the role of RASAL2 in CRC has been performed.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of RASAL2 promotes the proliferation, epithelial-mesenchymal transition and metastasis of colorectal cancer cells

et al. 2017

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Abstract. RAS protein activator like 2 (RASAL2) is a RAS-GTPase-activating protein and has recently been identified to be a tumor suppressor in various types of human cancer; however, the function of RASAL2 in colorectal carcinoma (CRC) remains unclear. In the present study, the function of RASAL2 in CRC cells was investigated using a RASAL2 loss-of-function cell model. RASAL2 short hairpin RNA was transfected into the human CRC cell lines LoVo, SW620 and HCT116, and the wild-type colon cell line NCM460. The subsequent downregulation of RASAL2 was evaluated using western blot and reverse transcription-quantitative polymerase chain reaction analyses. It was observed that RASAL2 expression was significantly decreased in human CRC tissues and cell lines (P<0.01). In the loss-of-function cell models, RASAL2 expression was decreased significantly, while cell proliferation, colony formation, migration and invasion were increased (all P<0.01). These effects were associated with the induction of epithelial-mesenchymal transition and Raf/mitogen-activated protein kinase hyperactivation. The results of the present study indicate that RASAL2 is a potential therapeutic target to inhibit CRC progression and metastasis.

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“…Gene expression inhibition by siRNA or shRNA reduced human tumor xenograft growth in mice and altered other tumor characteristics in, breast and bladdercell lines. Results indicate that RASAL2 (a tumor and metastasis suppressor) and NENF (a neuronderived neurotrophic factor) depletion interferes with Akt, Wnt and MAPK signaling pathways as well as regulation of epigenetic drivers ofgrowth and metastasis [75]. In addition, a new NGS-based method to identify somatic mutations has been used to do comprehensive mutation profiling in thirty genes found frequently mutated in lung adenocarcinoma.…”

Section: Omics Studies In Other Cancer Typesmentioning

confidence: 99%

The Promise of Single Cell Omics for Onco-therapy

Azizi¹,

Clouthier

Wicha³

2014

J Mol Genet Med

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Despite extensive research effort and considerable progress, the "war on cancer" that president Nixon declared in 1971 has yet to be optimally integrated into cancer therapeutics and as such cancer remains a major medical challenge for oncologists. The dynamic and complex biology of tumor cells undergoing clonal evolution generates cells with diverse degrees of drug resistance and metastatic potential. This highlights the need to be able to access this clonal density in order to develop effective therapeutics. With this prospective, early phase single cell studies are vital for thoroughly interrogating tumor heterogeneity to uncover more about cancer cell biology and to explore new therapeutic targets leading to more successful treatments. Current evidence supports the notion that clonogenic cells within the tumor mass may potentially give rise to a population of cells with unique genomic, transcriptomic and proteomic features distinct from the rest of the tumor mass. This observation can explain drug resistance after an initial period of primary tumor response. Therefore, completely abrogating or at a minimum achieving long-term, durable control over cancer requires researchers and oncologists to employ a personalized medicine approach that includes both tumor and patient-associated variables to modify current therapeutic regimens. In this review we discuss the importance of omics and in particular single cell genomics which are increasingly promising given recently developed technology advancements to facilitate exploration of cellular heterogeneity and tumor complexity. Keywords: Cancer genomics; Single cell; Tumor heterogeneity; Oncology therapy The Combinatorial Nature of CancerCancer is a catch all term for a collection of many related, but discrete diseases that share some degree of commonality, but can no longer be considered a single disease [1]. Although tumors may initiate following malignant transformation of even a single normal cell, more probably continuous genetic mutations and gene expression alterations during tumor progression lead to a metastatic phenotype composed of multiple subsets of tumor cells with distinct characteristics. In fact, each of the genetic and epigenetic events that happen to the tumor cells after tumor initiation result in a disease that collectively is termed cancer. Yet each discrete cancer shares certain characteristics with other malignancies. In this context, malignancy of tumor cells increase as a result of the cumulative formation of a series of tumor clones. Multi-step Cancer DevelopmentThe six elements of the model of multi-step cancer development [2] including uncontrolled proliferation, growth suppressor inactivation, cell death resistance, replicative immortality, angiogenesis induction and acquisition of an invasive and metastatic phenotype should be considered when defining a novel therapeutic regimen to eradicate primary and metastatic disease. Furthermore, these elements are important considerations for successful cancer therapy in the context propo...

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Genome-Wide Study of Hypomethylated and Induced Genes in Patients with Liver Cancer Unravels Novel Anticancer Targets

Cited by 92 publications

References 44 publications

Trm112, a Protein Activator of Methyltransferases Modifying Actors of the Eukaryotic Translational Apparatus

Trm112, a Protein Activator of Methyltransferases Modifying Actors of the Eukaryotic Translational Apparatus

Downregulation of RASAL2 promotes the proliferation, epithelial-mesenchymal transition and metastasis of colorectal cancer cells

The Promise of Single Cell Omics for Onco-therapy

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