Zhao et al. demonstrated that Let-7b regulates neural stem cell proliferation and differentiation by targeting cyclin D1 [39]. Our results also indicated that down-regulation of Let-7b was correlated with cisplatin resistance in glioblastoma cells, and Let-7b could attenuate cyclin D1 expression then dampen chemoresistance of U251R cells to cisplatin. Overall, restoration of Let-7 in glioblastoma may
offer a new approach for cancer treatment in the future. Cyclin D1 belongs to a family of protein kinases that involved in cell cycle regulation. Cyclin D1 has been proved to be associated with chemoresistance to cisplatin-based therapy. Noel et al. demonstrated that cyclin D1 expression was significantly higher in chemoresistant testicular germ tumor cell lines comparing with the parental cells. Furthermore, cyclin D1 knockdown in combination with cisplatin treatment Ferrostatin-1 nmr inhibited click here tumor cell growth more effectively than single treatments [40]. In pancreatic tumor cells, over-expression of cyclin D1 also dramatically reduced chemosensitivity and prolonged survival time upon cisplatin treatment, and knockdown of cyclin D1 resulted in impaired resistance to cisplatin-induced apoptosis [41, 42]. Moreover, inhibition of cyclin D1 expression in human pancreatic cancer cells enhances their responsiveness to multiple chemotherapeutic agents other than cisplatin, including 5-fluorouracil, 5-fluoro-2′-deoxyuridine, and mitoxantrone [43]These findings demonstrate
that up-regulation of cyclin D1 may be a major reason of cisplatin resistance in multiple tumors. In this regard, cyclin D1 could be a potential marker for treatment evaluation acetylcholine and a candidate
target to improve the treatment of cisplatin-resistant tumors. Our study indicated that Let-7b might down-regulate cyclin D1 protein expression through targeting its 3’-UTR. Therefore, cyclin D1 down-regulation induced by restoration of Let-7 in tumors might be a novel therapeutic strategy for cisplatin-resistant glioblastoma treatment. To sum up, we generated a cisplatin-resistant glioblastoma cell line U251R, and analyzed miRNA expression profiles in U251R compared with its parental cell line U251. Microarray data indicated that Let-7b was dramatically down-regulated in U251R cells compared with U251 cells. Furthermore, ectopic expression of Let-7b remarkably inhibited U251R cell chemoresistance to cisplatin through cyclin D1 expression blockade. Cyclin D1 knockdown significantly promoted cisplatin-induced apoptosis and G1 arrest. In conclusion, Let-7b could be considered as a novel marker of cisplatin resistance during early Palbociclib cost diagnosis, and more importantly, restoration of Let-7 in tumor cells could offer a novel therapeutic approach for cisplatin-resistant glioblastoma treatment. References 1. Furnari FB, Fenton T, Bachoo RM, et al.: Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 2007, 21:2683–2710.PubMedCrossRef 2.