miR-142–3p Down-Regulation Contributes to Thyroid Follicular Tumorigenesis by Targeting ASH1L and MLL1

Colamaio, Marianna; Puca, Francomichele; Ragozzino, Elvira; Gemei, Marica; Decaussin‐Petrucci, Myriam; Aiello, Concetta; Bastos, André Uchimura; Federico, Antonella; Chiappetta, Gennaro; Vecchio, Luigi Del; Torregrossa, Liborio; Battista, Sabrina; Fusco, Alfredo

doi:10.1210/jc.2014-2280

Cited by 52 publications

(45 citation statements)

References 38 publications

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“…Similar results were observed for miR-142-3p that also seems to play a tumor-suppressive role in the thyroid gland. Its downregulation in tumor was associated with the aberrant action of Trithorax group proteins, major regulators of the homeobox gene expression (77). Another study revealed an important role of miR-122 significantly upregulated in FTC compared with FA.…”

Section: The Potential Of Micrornas In Thyroid Cancer Treatmentmentioning

confidence: 96%

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

Wójcicka

Kolanowska

Jażdżewski

2016

European Journal of Endocrinology

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MicroRNAs, short non-coding regulators of the gene expression, are subjects of numerous investigations assessing their potential use in the diagnostics and management of human diseases. In this review, we focus on studies that analyze the utility of microRNAs as novel diagnostic and therapeutic tools in follicular cell-derived thyroid carcinomas. This very interesting and promising field brings new insight into future strategies for personalized medicine.

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Section: The Potential Of Micrornas In Thyroid Cancer Treatmentmentioning

confidence: 96%

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

Wójcicka

Kolanowska

Jażdżewski

2016

European Journal of Endocrinology

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“…In addition to its role in leukemia, ASH1L is overexpressed in a variety of solid tumors, including thyroid and breast cancer [87,88]. In thyroid cancer, ASH1L is overexpressed in tumor-specific truncated forms, although what parts of the protein are truncated or what processing events produce them has not been explored.…”

Section: Ash1l: Hox Gene Activator With Emerging Role In Cancermentioning

confidence: 99%

“…In thyroid cancer, ASH1L is overexpressed in tumor-specific truncated forms, although what parts of the protein are truncated or what processing events produce them has not been explored. Expression of the miRNA miR-142-3p suppresses ASH1L protein expression by binding to the ASH1L 3´UTR, an effect correlated with inhibition of colony formation and slowing of thyroid cancer cell growth [87]. Interestingly, in mouse embryonic stem cells ASH1L is regulated by a different miRNA, miR-290, which downregulates ASH1L expression and prevents aberrant overexpression of Hoxa, Hoxb, Hoxc and Hoxd genes [89].…”

Section: Ash1l: Hox Gene Activator With Emerging Role In Cancermentioning

confidence: 99%

“…Differentiating mouse embryonic stem cells lacking the ASH1L SET domain show a loss of expression of 152 genes, including members of the Hox and Wnt families [86]. Together, these studies suggest that targeted inhibition of ASH1L KMTase activity could be a potential therapeutic approach in cancers driven by high HOX expression.In addition to its role in leukemia, ASH1L is overexpressed in a variety of solid tumors, including thyroid and breast cancer [87,88]. In thyroid cancer, ASH1L is overexpressed in tumor-specific truncated forms, although what parts of the protein are truncated or what processing events produce them has not been explored.…”

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confidence: 99%

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H3K36 Methyltransferases as Cancer Drug Targets: Rationale and Perspectives for Inhibitor Development

2016

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Methylation at histone 3, lysine 36 (H3K36) is a conserved epigenetic mark regulating gene transcription, alternative splicing and DNA repair. Genes encoding H3K36 methyltransferases (KMTases) are commonly overexpressed, mutated or involved in chromosomal translocations in cancer. Molecular biology studies have demonstrated that H3K36 KMTases regulate oncogenic transcriptional programs. Structural studies of the catalytic SET domain of H3K36 KMTases have revealed intriguing opportunities for design of small molecule inhibitors. Nevertheless, potent inhibitors for most H3K36 KMTases have not yet been developed, underlining the challenges associated with this target class. As we now have strong evidence linking H3K36 KMTases to cancer, drug development efforts are predicted to yield novel compounds in the near future. Cellular development and differentiation are controlled by post-translational modifications on DNA and histone proteins, forming an epigenetic (above the genes) regulatory network. Disruption of epigenetic pathways is a nearly universal feature of cancer, causing aberrations in gene expression and genome integrity (reviewed in [1]). A key group of epigenetic enzymes disrupted in cancer is the lysine methyltransferases (KMTases), which install methyl groups on histone proteins. In cancer cells, methylation performed by KMTases drives proliferation and halts differentiation by modifying gene transcription and other DNA-templated processes [2][3][4]. Over the past decade, KMTases have emerged as important drug targets for both industrial and academic research groups. Some progress has been made, most notably by selective inhibitors for the EZH2 and DOT1L KMTases that have reached clinical trials for the treatment of nonHodgkin lymphoma and acute leukemia, respectively [5,6]. Nevertheless, selective and cell permeable inhibitors for many KMTases remain unavailable.Methylation at H3K36 represents a particularly important chromatin mark implicated in diverse forms of cancer. KMTases with specificity toward H3K36 are overexpressed in cancer cells and have been characterized as regulators of cell growth, differentiation, stemness and DNA repair pathways [7][8][9]. However, very few selective and cell-active small molecule inhibitors of H3K36-specfic KMTases have been reported to date. In this article, we provide an overview of cellular pathways involving H3K36 methylation and discuss the diverse functions carried out by the eight different human H3K36-specific KMTases. Then we analyze structural characteristics of the catalytic SET domain of H3K36 KMTases and evaluate prospects for their inhibition by small molecules. Review Rogawski, Grembecka & Cierpicki We conclude with a discussion of the challenges and o pportunities for targeting these proteins. SPECIAL FOCUS y Epigenetic drug discovery H3K36 methylation regulates diverse processes implicated in cancerH3K36 methylation participates in a wide variety of nuclear pathways. Many of these processes, including transcriptional regulation, alternative spli...

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“…miR-142-3p has been reported to be downregulated in diverse types of cancer, including leukemia, thyroid follicular carcinomas, cervical cancer, hepatic cancer, glioblastoma, osteosarcoma and non-small cell lung cancer (16)(17)(18)(19)(20)(21)(22). miR-142-3p has been demonstrated to contribute to carcinogenesis by regulating cell cycle, cell migration, apoptosis and invasion by targeting various signaling pathways and…”

Section: Introductionmentioning

confidence: 99%

Downregulation of microRNA‑142‑3p and its tumor suppressor role in gastric cancer

et al. 2018

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miR-142–3p Down-Regulation Contributes to Thyroid Follicular Tumorigenesis by Targeting ASH1L and MLL1

Abstract: These data demonstrate that miR-142-3p downregulation has a role in thyroid tumorigenesis, by regulating ASH1L and MLL1.

Cited by 52 publications

References 38 publications

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

H3K36 Methyltransferases as Cancer Drug Targets: Rationale and Perspectives for Inhibitor Development

Downregulation of microRNA‑142‑3p and its tumor suppressor role in gastric cancer

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