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New discoveries of mdig in the epigenetic regulation of cancers.

ABSTRACT: Mineral dust-induced gene (mdig) encodes a member of the evolutionarily conserved JmjC family proteins that play fundamental roles in regulating chromatin-based processes as well as transcription of the genes in eukaryotic cells. This gene is also named as myc-induced nuclear antigen 53 (MINA), nucleolar protein 52 (NO52) and ribosomal oxygenase 2 (RIOX2). Increased expression of mdig had been noted in a number of human cancers, esp. lung cancer. Emerging evidence suggests that the oncogenic activity of mdig is most likely achieved through its regulation on the demethylation of histone proteins, despite it lacks the structural identities of the demethylases. Here, we discuss the latest discoveries on the characteristics of the mdig protein and its roles in a wide variety of normal and carcinogenic processes. We will also provide perspectives on how mdig is involved in the maintenance and differentiation of the embryonic stem cells, somatic stem cells and cancer stem cells.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6844078 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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New discoveries of mdig in the epigenetic regulation of cancers.

Zhang Qian Q Thakur Chitra C Shi Junwei J Sun Jiaying J Fu Yao Y Stemmer Paul P Chen Fei F

Seminars in cancer biology 20190702

Mineral dust-induced gene (mdig) encodes a member of the evolutionarily conserved JmjC family proteins that play fundamental roles in regulating chromatin-based processes as well as transcription of the genes in eukaryotic cells. This gene is also named as myc-induced nuclear antigen 53 (MINA), nucleolar protein 52 (NO52) and ribosomal oxygenase 2 (RIOX2). Increased expression of mdig had been noted in a number of human cancers, esp. lung cancer. Emerging evidence suggests that the oncogenic act ...[more]

PMID: 31276784

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Project description:Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evidence has shown the oncogenic capacity of E6, E7, and E5 genes of high-risk HPV. Interestingly, transcriptomic analysis has revealed that although a vast majority of the human genome is transcribed into RNAs, only 2% of transcripts are translated into proteins. The remaining transcripts lacking protein-coding potential are called non-coding RNAs. In addition to the transfer and ribosomal RNAs, there are regulatory non-coding RNAs classified according to size and structure in long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small RNAs; such as microRNAs (miRNAs), piwi-associated RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and endogenous short-interfering RNAs. Recent evidence has shown that lncRNAs, miRNAs, and circRNAs are aberrantly expressed under pathological conditions such as cancer. In addition, those transcripts are dysregulated in HPV-related neoplasms, and their expression correlates with tumor progression, metastasis, poor prognosis, and recurrence. Nuclear lncRNAs are epigenetic regulators involved in controlling gene expression at the transcriptional level through chromatin modification and remodeling. Moreover, disruption of the expression profiles of those lncRNAs affects multiple biological processes such as cell proliferation, apoptosis, and migration. This review highlights the epigenetic alterations induced by HPV, from infection to neoplastic transformation. We condense the epigenetic role of non-coding RNA alterations and their potential as biomarkers in transformation's early stages and clinical applications. We also summarize the molecular mechanisms of action of nuclear lncRNAs to understand better their role in the epigenetic control of gene expression and how they can drive the malignant phenotype of HPV-related neoplasia. Finally, we review several chemical and epigenetic therapy options to prevent and treat HPV-associated neoplasms.

Project description:Epigenetics is a growing field and in bladder cancer, it is of particular interest in advanced or metastatic disease. As opposed to genetic mutations in which the nucleotide sequence itself is altered, epigenetic alterations refer to changes to the genome that do not involve nucleotides. This is of great interest in cancer research because epigenetic alterations are reversible, making them a promising target for pharmacological agents. While chemoimmunotherapy is the mainstay for metastatic disease, there are few alternatives for patients who have progressed on first- or second-line treatment. By targeting reversible epigenetic alterations, novel epigenetic therapies are important potential treatment options for these patients. A search of clinical registries was performed in order to identify and collate epigenetic therapies currently in human trials. A literature search was also performed to identify therapies that are currently in preclinical stages, whether this be in vivo or in vitro models. Twenty-five clinical trials were identified that investigated the use of epigenetic inhibitors in patients with bladder cancer, often in combination with another agent, such as platinum-based chemotherapy or pembrolizumab. The main classes of epigenetic inhibitors studied include DNA-methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, and histone methyltransferase (HMT) inhibitors. At present, no phase 3 clinical trials have been registered. Few trials have published results, though DNMT inhibitors have shown the most promise thus far. Many patients with advanced or metastatic bladder cancer have limited treatment options, particularly when first- or second-line chemoimmunotherapy fails. Epigenetic alterations, which are common in bladder cancer, are potential targets for drug therapies, and these epigenetic agents are already in use for many cancers. While they have shown promise in pre-clinical trials for bladder cancer, more research is needed to assess their benefit in clinical settings.

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New discoveries of mdig in the epigenetic regulation of cancers.

Publications

New discoveries of mdig in the epigenetic regulation of cancers.

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