https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/33 Principal Investigator- Dr. Sandeep Saxena Fri, 03 Apr 2026 17:06:31 GMT 2026-04-03T17:06:31Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1370 Title: Sld5 Ensures Centrosomal Resistance to Congression Forces by Preserving Centriolar Satellites Authors: Saxena, Sandeep; Kaur, Manpreet; Devi, Raksha; Ghosh, Tanushree; Khan, Md Muntaz; Kumar, Praveen; Kar, Ananya; Sharma, Aparna; Varshney, Akhil; Kumar, Vipin Abstract: The migration of chromosomes during mitosis is mediated primarily by kinesins that bind to the chromosomes and move along the microtubules, exerting pulling and pushing forces on the centrosomes. We report that a DNA replication protein, Sld5, localizes to the centrosomes, resisting the microtubular pulling forces experienced during chromosome congression. In the absence of Sld5, centriolar satellites, which normally cluster around the centrosomes, are dissipated throughout the cytoplasm, resulting in the loss of their known function of recruiting the centrosomal protein, pericentrin. We observed that Sld5-deficient centrosomes lacking pericentrin were unable to endure the CENP-E- and Kid-mediated microtubular forces that converge on the centrosomes during chromosome congression, resulting in monocentriolar and acentriolar spindle poles. The minus-end-directed kinesin-14 motor protein, HSET, sustains the traction forces that mediate centrosomal fragmentation in Sld5-depleted cells. Thus, we report that a DNA replication protein has an as yet unknown function of ensuring spindle pole resistance to traction forces exerted during chromosome congression. Sun, 01 Jan 2017 00:00:00 GMT https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1370 2017-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1061 Title: The microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expression Authors: Saxena, Sandeep; Nagarajan, Perumal; Khan, Md. Muntaz; Ghosh, Tanushree; Kumar, Praveen; Priyanka, Priyanka; Shekhar, Ritu Abstract: MicroRNAs of the miR-16 and miR-34 families have been reported to inhibit cell cycle progression, and their loss has been linked to oncogenic transformation. Utilizing a high-throughput, genome-wide screen for miRNAs and mRNAs that are differentially regulated in osteosarcoma (OS) cell lines, we report that miR-449a and miR-424, belonging to the miR-34 and miR-16 families, respectively, target the major S/G2 phase cyclin, cyclin A2 (CCNA2), in a bipartite manner. We found that the 3'-UTR of CCNA2 is recognized by miR-449a, whereas the CCNA2 coding region is targeted by miR-424. Of note, we observed loss of both miR-449a and miR-424 in OS, resulting in derepression of CCNA2 and appearance of aggressive cancer phenotypes. Ectopic expression of miR-449a and miR-424 significantly decreased cyclin A2 levels and inhibited proliferation rate, migratory potential, and colony-forming ability of OS cells. To further probe the roles of miR-449a and miR-424 in OS, we developed an OS mouse model by intraosseous injection of U2OS cells into the tibia bone of NOD-scid mice, which indicated that miR-449a and miR-424 co-expression suppresses tumor growth. On the basis of this discovery, we analyzed the gene expression of human OS biopsy samples, revealing that miR-449a and miR-424 are both down-regulated, whereas cyclin A2 is significantly up-regulated in these OS samples. In summary, the findings in our study highlight that cyclin A2 repression by miRNAs of the miR-16 and miR-34 families is lost in aggressive OS. Tue, 01 Jan 2019 00:00:00 GMT https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1061 2019-01-01T00:00:00Z