It is known that thyroid hormone is an important regulator of cancer development and metastasis. What is more, changes across the genome, as well as alternative splicing, may affect the activity of ...the thyroid hormone receptors. Mechanism of action of the thyroid hormone is different in every cancer; therefore in this review thyroid hormone and its receptor are presented as a regulator of renal cell carcinoma.
Mitochondrial diseases are defined by a respiratory chain dysfunction and in most of the cases manifest as multisystem disorders with predominant expression in muscles and nerves and may be caused by ...mutations in mitochondrial (mtDNA) or nuclear (nDNA) genomes. Most of the proteins involved in respiratory chain function are nuclear encoded, although 13 subunits of respiratory chain complexes (together with 2 rRNAs and 22 tRNAs necessary for their translation) encoded by mtDNA are essential for cell function. nDNA encodes not only respiratory chain subunits but also all the proteins responsible for mtDNA maintenance, especially those involved in replication, as well as other proteins necessary for the transcription and copy number control of this multicopy genome. Mutations in these genes can cause secondary instability of the mitochondrial genome in the form of depletion (decreased number of mtDNA molecules in the cell), vast multiple deletions or accumulation of point mutations which in turn leads to mitochondrial diseases inherited in a Mendelian fashion. The list of genes involved in mitochondrial DNA maintenance is long, and still incomplete.
The physiological significance and metabolism of oligoadenylated and polyadenylated human mitochondrial mRNAs are not known to date. After study of eight mitochondrial transcripts (ND1, ND2, ND3, ...ND5, CO1, CO2, ATP6/8 and Cyt. b) we found a direct correlation between the half-lives of mitochondrial mRNAs and their steady-state levels. Investigation of the mt-mRNA decay after thiamphenicol treatment indicated that three transcripts (ND2, ND3 and Cyt. b) are significantly stabilized after inhibition of mitochondrial translation. Careful analysis one of them, ND3, showed that inaccurate processing of the H-strand RNA precursor may occasionally occur between the ND3 and tRNA(Arg) locus leading to synthesis of ND3 mRNAs lacking the STOP codon. However, analysis of the oligo(A) fraction observed in case of the ND3 indicates that partially polyadenylated mRNAs are linked rather to the transcription process than to the translation-dependent deadenylation. Analysis of ND3 mRNA turnover in cells with siRNA-mediated knock-down of the mitochondrial poly(A) polymerase shows that strongly decreased polyadenylation does not markedly affect the decay of this transcript. We present a model where oligoadenylated mitochondrial transcripts are precursors of molecules containing full length poly(A) tails.
Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the ...other hand, there is emerging evidence on the use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA status in VSCC patients, haplogroup distribution analysis and D-loop sequencing were performed. The results were compared with available data for the general Polish population, cancer free-centenarians as well as patients with endometrial and head and neck cancer. The obtained data were also compared with the current status of mitochondrial databases. Significant differences in haplogroup distribution between VSCC cohort, general Polish population and cancer-free centenarians cohort were found. Moreover, a correlation between the VSCC patients haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA polymorphisms was found in VSCC. Our results suggest that the mitochondrial genetic background may influence the risk of VSCC occurrence as well as susceptibility to HPV infection.
Glaucoma is one of the leading causes of visual impairment and blindness worldwide. However, the cause of retinal ganglion cell loss and damage of the optic nerve in its pathogenesis is largely ...unknown. The high energy demands of these cells may reflect their strong dependence on mitochondrial function and thus sensitivity to mitochondrial defects. To address this issue, we studied whole mitochondrial genome variation in normal tension glaucoma patients and control individuals from the Polish population using next generation sequencing. Our findings indicate that few features of mitochondrial DNA variation are different for glaucoma patients and control subjects. New insights into normal tension glaucoma development are discussed. We provide also a comprehensive approach for mitochondrial DNA analysis and variant evaluation.
•Large-scale deletions of mtDNA were not common in blood of NTG patients.•Mitochondrial haplogroup H1 was significantly associated with NTG.•NTG cohort exhibited a higher total load of rare mtDNA variants, and in particular in MT-ND6 gene, compared to controls.•Rare coding variants were commonly detected in both groups with no difference in the possibly pathogenic variant load.•A m.12705C > T and m.310T > C variants were less prevalent in NTG patients suggesting they may be protective factors.
Leber's hereditary optic neuropathy (LHON) was the first human disease found to be associated with a mitochondrial DNA (mtDNA) point mutation. The most common LHON mutations are 11778G>A, 3460G>A or ...14484T>C. The most common clinical features of LHON are optic nerve and retina atrophy. The affected tissue is not available for studies, therefore a variety of other cell types are used. However, all models face difficulties and limitations in mitochondrial disease research. The advantages and disadvantages of different cell models used to study LHON, recent advances in animal model generation and novel approaches in this field are discussed.
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