Carcinogenesis is a multilevel process characterized by genetic and epigenetic alterations,thus contributing to uncontrolled proliferation that eventually leads to cancer.The process of carcinogenesis involves an intr...Carcinogenesis is a multilevel process characterized by genetic and epigenetic alterations,thus contributing to uncontrolled proliferation that eventually leads to cancer.The process of carcinogenesis involves an intricate dis-orchestration in the expression of both,coding and non-coding sequences and is also dependent on the reprogramming of energy metabolism as both direct and indirect consequence of oncogenic mutations.Dysregulated mitochondrial energetics is an important hallmark of cancer,where cancer cells switch to the glycolytic pathway as an alternate source of energy to support the continuous energy supply needed for their indefinite growth.Even though functional mitochondria are indispensable for cancer cells,cancer cells exhibit different bioenergetics transitions based on the development status of cells undergoing carcinogenesis.Although the role of coding sequences in regulating energy metabolism shift is well studied,the role of non-coding sequences in modulating energy metabolism is still unclear.MicroRNAs(miRNAs),usually present in the nucleus and cytoplasm,have now been reported to localize in the mitochondria also known as,mitochondrial miRNAs(MitomiRs),which can originate either from the nuclear or mitochondrial genome.MitomiRs are reported to be associated with both oncogenic and tumor-suppressive functions.MitomiRs can target metabolic pathway-related protein-coding genes to alter cellular metabolism and promote carcinogenesis.Several mitomiRs like miR-1,miR-133,miR-128,and miR-21 have been reported to be involved in normal physiology,survival,and pathology.Since energy metabolism is one of the most important hallmarks of carcinogenesis and its underlying mechanism involves dysregulation of mitochondrial metabolism,we have tried to collate the importance of mitomiRs in the process of cancer energy metabolism and carcinogenesis.展开更多
Telomere, the nucleoprotein structure at the end of eukaryotic linear chromosomes is indispensable for maintaining the genome stability. Telomeric DNA loss is apparent with each cell division, which marks an endpoint ...Telomere, the nucleoprotein structure at the end of eukaryotic linear chromosomes is indispensable for maintaining the genome stability. Telomeric DNA loss is apparent with each cell division, which marks an endpoint to the indefinite replication of the cell by causing replicative senescence that may lead to the programmed cell death. The loss of telomere is normal in cell division and as such after 20 - 40 divisions, telomere becomes too short to facilitate the capping function. Telomere uncapping or chromosomal free end causes a potential threat to the genomic stability and thus leads to the accumulation of chromosomal abnormalities that have been known to play a role in aging and cancer. Telomerase, the ribonucleoprotein complex, and its accessory proteins are required to maintain the telomere sequence. Telomerase plays a key role in maintaining the length of telomere by adding G-rich repeat sequences. Its activity has been found to be quite high in the gametes, stem cells and most importantly tumor cells. Almost 85% of tumor cells compensate for telomere loss aided by telomerase-associated protein complex and shelter in complex or telosome. However, 5% - 10% of the cells undergo telomerase-independent mechanism. This review presents the molecular view of the telomere and telomerase along with its associated complex structures. It also discusses its contrasting role in causing cellular senescence and promoting tumorigenesis.展开更多
文摘Carcinogenesis is a multilevel process characterized by genetic and epigenetic alterations,thus contributing to uncontrolled proliferation that eventually leads to cancer.The process of carcinogenesis involves an intricate dis-orchestration in the expression of both,coding and non-coding sequences and is also dependent on the reprogramming of energy metabolism as both direct and indirect consequence of oncogenic mutations.Dysregulated mitochondrial energetics is an important hallmark of cancer,where cancer cells switch to the glycolytic pathway as an alternate source of energy to support the continuous energy supply needed for their indefinite growth.Even though functional mitochondria are indispensable for cancer cells,cancer cells exhibit different bioenergetics transitions based on the development status of cells undergoing carcinogenesis.Although the role of coding sequences in regulating energy metabolism shift is well studied,the role of non-coding sequences in modulating energy metabolism is still unclear.MicroRNAs(miRNAs),usually present in the nucleus and cytoplasm,have now been reported to localize in the mitochondria also known as,mitochondrial miRNAs(MitomiRs),which can originate either from the nuclear or mitochondrial genome.MitomiRs are reported to be associated with both oncogenic and tumor-suppressive functions.MitomiRs can target metabolic pathway-related protein-coding genes to alter cellular metabolism and promote carcinogenesis.Several mitomiRs like miR-1,miR-133,miR-128,and miR-21 have been reported to be involved in normal physiology,survival,and pathology.Since energy metabolism is one of the most important hallmarks of carcinogenesis and its underlying mechanism involves dysregulation of mitochondrial metabolism,we have tried to collate the importance of mitomiRs in the process of cancer energy metabolism and carcinogenesis.
文摘Telomere, the nucleoprotein structure at the end of eukaryotic linear chromosomes is indispensable for maintaining the genome stability. Telomeric DNA loss is apparent with each cell division, which marks an endpoint to the indefinite replication of the cell by causing replicative senescence that may lead to the programmed cell death. The loss of telomere is normal in cell division and as such after 20 - 40 divisions, telomere becomes too short to facilitate the capping function. Telomere uncapping or chromosomal free end causes a potential threat to the genomic stability and thus leads to the accumulation of chromosomal abnormalities that have been known to play a role in aging and cancer. Telomerase, the ribonucleoprotein complex, and its accessory proteins are required to maintain the telomere sequence. Telomerase plays a key role in maintaining the length of telomere by adding G-rich repeat sequences. Its activity has been found to be quite high in the gametes, stem cells and most importantly tumor cells. Almost 85% of tumor cells compensate for telomere loss aided by telomerase-associated protein complex and shelter in complex or telosome. However, 5% - 10% of the cells undergo telomerase-independent mechanism. This review presents the molecular view of the telomere and telomerase along with its associated complex structures. It also discusses its contrasting role in causing cellular senescence and promoting tumorigenesis.
