Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer

Diquigiovanni, Chiara; Bergamini, Christian; Evangelisti, Cecilia; Isidori, Federica; Vettori, Andrea; Tiso, Natascia; Argenton, Francesco; Costanzini, Anna; Iommarini, Luisa; Anbunathan, Hima; Pagotto, Uberto; Repaci, Andrea; Babbi, Giulia; Casadio, Rita; Lenaz, Giorgio; Rhoden, Kerry J.; Porcelli, Anna Maria; Fato, Romana; Bowcock, Anne M.; Seri, Marco; Romeo, Giovanni; Bonora, Elena

doi:10.1002/ijc.31548

Cited by 38 publications

(34 citation statements)

References 45 publications

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“…A recent study has shown that mutated MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer [67]. This arises due to a mutated MYO1F gene at the TCO locus (Gly134Ser) that leads to increased oncogenic potential in vitro in terms of cell growth and invasion.…”

Section: Myo1fmentioning

confidence: 99%

“…However, in the mutant cell lines, analysis by live-cell visualization revealed that the mitochondria appeared as separate rod-shaped organelles with increased mass that produced significantly more intracellular and extracellular reactive oxygen species. How MYO1F regulates the mitochondrial network needs to be addressed.Several somatic mutations in MYO1F related to different types of cancer have been found in genetic databases [67]. One example is the fusing of the mixed lineage leukemia gene with the MYO1F gene, which has been described as recurrent in infant acute monocytic leukemia [68,69].…”

Section: Myo1fmentioning

confidence: 99%

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Long-Tailed Unconventional Class I Myosins in Health and Disease

Navinés-Ferrer

Martı́n

2020

IJMS

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Long-tailed unconventional class I myosin, Myosin 1E (MYO1E) and Myosin 1F (MYO1F) are motor proteins that use chemical energy from the hydrolysis of adenosine triphosphate (ATP) to produce mechanical work along the actin cytoskeleton. On the basis of their motor properties and structural features, myosins perform a variety of essential roles in physiological processes such as endocytosis, exocytosis, cell adhesion, and migration. The long tailed unconventional class I myosins are characterized by having a conserved motor head domain, which binds actin and hydrolyzes ATP, followed by a short neck with an isoleucine-glutamine (IQ) motif, which binds calmodulin and is sensitive to calcium, and a tail that contains a pleckstrin homology domain (PH), a tail homology 1 domain (TH1), wherein these domains allow membrane binding, a tail homology 2 domain (TH2), an ATP-insensitive actin-binding site domain, and a single Src homology 3 domain (SH3) susceptible to binding proline rich regions in other proteins. Therefore, these motor proteins are able to bind actin, plasma membrane, and other molecules (adaptor, kinases, membrane proteins) that contribute to their function, ranging from increasing membrane tension to molecular trafficking and cellular adhesion. MYO1E and MYO1F function in host self-defense, with a better defined role in innate immunity in cell migration and phagocytosis. Impairments of their function have been identified in patients suffering pathologies ranging from tumoral processes to kidney diseases. In this review, we summarize our current knowledge of specific features and functions of MYO1E and MYO1F in various tissues, as well as their involvement in disease.

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Section: Myo1fmentioning

confidence: 99%

Section: Myo1fmentioning

confidence: 99%

Long-Tailed Unconventional Class I Myosins in Health and Disease

Navinés-Ferrer

Martı́n

2020

IJMS

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“…It has been demonstrated that the overall heritability of thyroid cancer is high compared with other cancers 4–7. Classic linkage studies in familial papillary thyroid cancer have revealed a small number of culpable loci; however, heritable germline pathogenic variants have been largely absent from familial and sporadic cases 8–19. Therefore, we hypothesised that the genetic risk predisposing to thyroid cancer is due to complex genetic factors and a combination of low penetrance alleles.…”

Section: Introductionmentioning

confidence: 98%

Variants in LRRC34 reveal distinct mechanisms for predisposition to papillary thyroid carcinoma

Comiskey

Liyanarachchi

et al. 2020

J Med Genet

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BackgroundPapillary thyroid carcinoma (PTC) demonstrates high heritability and a low somatic mutation burden relative to other cancers. Therefore, the genetic risk predisposing to PTC is likely due to a combination of low penetrance variants. A recent genome-wide association study revealed the association of PTC with a missense variant, rs6793295, at 3q26 in a gene called Leucine Repeat Rich Containing 34 (LRRC34).MethodsWe report the mechanisms of PTC risk at 3q26 using a combination of overexpression, mass spectroscopy, knockdown, transcriptome profiling, migration assays and genetic analysis.ResultsWe observed differential binding of wild-type and missense LRRC34 to RANBP1. Overexpression of missense LRRC34 reduced RanGTP levels and increased apoptosis. We also identified a second linkage disequilibrium (LD) block upstream of LRRC34 containing regulatory variants with allele-specific expression. Transcriptome profiling of LRRC34 knockdown cells showed changes in genes involved with cellular movement. LRRC34 knockdown reduced the migration of thyroid cancer cell lines. Lastly, we assessed the relative contribution of PTC risk from each locus using haplotype analysis.ConclusionsOur study demonstrates two separate mechanisms, one in G protein signalling and the other in transcriptional control, dictating PTC risk at 3q26 using both biochemical and genetic techniques.

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“…In general, TC has few obvious symptoms and is usually found by neck examination. Such cancer has a tendency of family aggregation, but its genetic basis is not totally clear [4] . At present, TC is mainly divided into four categories, namely papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC).…”

Section: Introductionmentioning

confidence: 99%

Excavating thyroid carcinoma risk metabolic genes associated with biological clock by bioinformatics analysis: A study based on TCGA and GEO data

wang

Zhang

Liu

et al. 2020

Preprint

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Background Thyroid carcinoma (TC) is malignant tumor of the endocrine gland with a significantly increased incidence in recent years, which related to metabolic diseases and biological clock disorder. The molecular mechanism and risk metabolic genes associated with biological clock of TC require conducting study. Methods We mined differentially expressed genes of TC (TC-DEGs) from TCGA and GEO database. Searching for biorhythm related genes (BRGs) based on core clock genes by STRING analysis. Next, we used a series of bioinformatics methods to analyze the TC-DEGs and BRGs, including chromosome location, GO and KEGG pathway annotation. Then, we extracted the expression of statistically significant TC metabolic genes by Perl program combined with a computational method of GSEA. Furthermore, screen the risk metabolic genes and reveal potential underlying KEGG pathways of the gene signatures. Results Our results identified 474 DEGs (P < 0.05; |log FC| > 1) in patients with TC compared with the normal controls using the available numerical mRNA expression values. The chromosomal assignments of TC-DEGs and BRGs were inhomogeneous. These genes were mainly distributed on Chrom01, 02, 11, 12, 04, 03 and X, none of the associated genes were distributed on sex Y chromosome. ARNTL and BHLHE40 belong to both the TC-DEGs and BRGs. PER2, NCOR1, RXRG, CCND1, SERPINE1 and PLAU were mined which act as the hub of signaling pathways linking “Thyroid hormone signaling pathway”, “Circadian rhythm”, “Transcriptional misregulation in cancer” and so on. One hundred and forty-one metabolic genes were extracted to train the prognostic model, and 11 risk genes were found, among them, 10 risk gene products have indirect interaction with ARNTL and BHLHE40. Such important genes for TC were regulated by many common conserved microRNAs. Conclusions Our study identified 8 key genes and 11 risk metabolic genes of thyroid carcinoma associated with biological clock by bioinformatics analysis. And the coding products of these genes form a clear interaction network, which is conducive to further study the molecular mechanism, reveal the role of circadian clock genes and metabolic genes in thyroid cancer.

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Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer

Cited by 38 publications

References 45 publications

Long-Tailed Unconventional Class I Myosins in Health and Disease

Long-Tailed Unconventional Class I Myosins in Health and Disease

Variants in LRRC34 reveal distinct mechanisms for predisposition to papillary thyroid carcinoma

Excavating thyroid carcinoma risk metabolic genes associated with biological clock by bioinformatics analysis: A study based on TCGA and GEO data

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