MicroRNAs
MicroRNAs (miRNA) have been implicated in the epigenetic regulation of cancer cells and the following miRNAs have been identified in tumor-related functions in osteosarcoma. Hypoxia-inducible factor-2α (HIF-2α) promoter upstream transcript (HIF2PUT) is a novel long non-coding RNA (lncRNA); overexpression of HIF2PUT markedly decreased the percentage of CD133-expressing cells and impaired OSC sphere-forming capacity in MG63 osteosarcoma cells [49]. Silencing miR-133a reduced cell invasion and prolonged survival in osteosarcoma-bearing mice, suggesting that miR-133a may play a role in OSC regulation [50]. A total of 189 miRNAs were reported to be differentially expressed in 3AB-OS CSCs relative to their parental cells. These included two miRNA families, let-7/98 and miR-29a, b, c, and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2 and GHR), suggesting they may comprise a set of OSC markers [51]. MiR-29b-1 was found to negatively regulate expressions of CD133, N-Myc, Oct3/4, Sox2 and Nanog in OSCs; in contrast overexpression of miR-29b-1 consistently reduced growth and the sphere-forming ability of OSCs in this cell line [52].
Telomerase and DNA repair
Telomerase activity has been detected in most malignant cancer cells, including osteosarcoma, and is crucial for the maintenance of stem/progenitor cells. However the relationship between telomerase expression and CSCs remains unclear [71]. High telomerase activity has been linked to enhanced stem cell-like properties in osteosarcoma cells, including sphere-forming capacity, invasiveness, metastatic potential and resistance to chemotherapeutic agents [53]. In addition, sphere-driving OSCs displayed increased expressions of CD117 and Stro-1 compared to telomerase-negative cells; conversely inhibition of telomerase resulted in decreased tumorigenic potential in osteosarcoma [53]. Increased expression of DNA repair enzyme genes, MLH1 and MSH2, has also been linked to chemoresistance in osteosarcoma sphere cells [13].
MicroRNAsMicroRNAs (miRNA) have been implicated in the epigenetic regulation of cancer cells and the following miRNAs have been identified in tumor-related functions in osteosarcoma. Hypoxia-inducible factor-2α (HIF-2α) promoter upstream transcript (HIF2PUT) is a novel long non-coding RNA (lncRNA); overexpression of HIF2PUT markedly decreased the percentage of CD133-expressing cells and impaired OSC sphere-forming capacity in MG63 osteosarcoma cells [49]. Silencing miR-133a reduced cell invasion and prolonged survival in osteosarcoma-bearing mice, suggesting that miR-133a may play a role in OSC regulation [50]. A total of 189 miRNAs were reported to be differentially expressed in 3AB-OS CSCs relative to their parental cells. These included two miRNA families, let-7/98 and miR-29a, b, c, and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2 and GHR), suggesting they may comprise a set of OSC markers [51]. MiR-29b-1 was found to negatively regulate expressions of CD133, N-Myc, Oct3/4, Sox2 and Nanog in OSCs; in contrast overexpression of miR-29b-1 consistently reduced growth and the sphere-forming ability of OSCs in this cell line [52].Telomerase and DNA repairTelomerase activity has been detected in most malignant cancer cells, including osteosarcoma, and is crucial for the maintenance of stem/progenitor cells. However the relationship between telomerase expression and CSCs remains unclear [71]. High telomerase activity has been linked to enhanced stem cell-like properties in osteosarcoma cells, including sphere-forming capacity, invasiveness, metastatic potential and resistance to chemotherapeutic agents [53]. In addition, sphere-driving OSCs displayed increased expressions of CD117 and Stro-1 compared to telomerase-negative cells; conversely inhibition of telomerase resulted in decreased tumorigenic potential in osteosarcoma [53]. Increased expression of DNA repair enzyme genes, MLH1 and MSH2, has also been linked to chemoresistance in osteosarcoma sphere cells [13].
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MicroRNAs microRNAs (miRNA) have been implicated in the epigenetic Regulation of Cancer cells have been identified and the following miRNAs in tumor-related functions in osteosarcoma. Hypoxia-inducible factor-2α (HIF-2α) promoter upstream transcript (HIF2PUT) is a novel long non-coding RNA (lncRNA); overexpression of HIF2PUT markedly decreased the percentage of CD133-expressing cells and impaired OSC sphere-forming capacity in MG63 osteosarcoma cells [49]. Silencing miR-133a reduced cell invasion and prolonged survival in osteosarcoma-bearing mice, suggesting that miR-133a may play a role in OSC regulation [50]. A total of 189 miRNAs were reported to be differentially expressed in 3AB-OS CSCs relative to their parental cells. These included two miRNA families, let-7/98 and miR-29a, b, c, and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2 and GHR), suggesting they may comprise a set of OSC markers [51]. . MiR-29b-1 was found to negatively regulate expressions of CD133, N-Myc, Oct3 / 4, Sox2 and Nanog in OSCs; in contrast overexpression of miR-29b-1 consistently reduced growth and the Sphere-Forming ability of OSCs in this Cell line [52]. Telomerase and DNA Repair Telomerase Activity has been detected in Most malignant Cancer cells, including osteosarcoma, and is CRUCIAL for. the maintenance of stem / progenitor cells. However the relationship between telomerase expression and CSCs remains unclear [71]. High telomerase activity has been linked to enhanced stem cell-like properties in osteosarcoma cells, including sphere-forming capacity, invasiveness, metastatic potential and resistance to chemotherapeutic agents [53]. In addition, sphere-driving OSCs displayed increased expressions of CD117 and Stro-1 compared to telomerase-negative cells; conversely inhibition of telomerase resulted in decreased tumorigenic potential in osteosarcoma [53]. Increased expression of DNA repair enzyme genes, MLH1 and MSH2, has also been linked to chemoresistance in osteosarcoma sphere cells [13].
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