ABSTRACT
Chemoresistance is still a major obstacle for lung cancer treatment. Increasing studies have demonstrated that microRNAs (miRNAs) are essential meditators of chemoresistance during cancer progression. MiR-451a is reported to be a tumor suppressor during cancer development. However, its effects on lung cancer and drug resistance in lung cancer are still unclear. In the study, the results showed that miR-451a exhibited a significant role in suppressing the drug resistance in lung cancer cells when treated with doxorubicin (DOX) through alleviating epithelialmesenchymal transition (EMT), as evidenced by the markedly reduced expression of N-cadherin and Vimentin, while the enhanced expression of E-cadherin. In addition, miR-451a over-expression markedly promoted the sensitivity of lung cancer cells to DOX treatments, and also disrupted the EMT of lung cancer cells. Mechanistically, miR-451a was found to directly target c-Myc to affect the EMT and drug resistance in lung cancer cells in response to DOX incubation. Furthermore, c-Myc knockdown markedly elevated the sensitivity of lung cancer cells to DOX, whereas over-expressing c-Myc markedly reversed the anti-tumor role of DOX, which was slightly diminished by miR-451a mimic. The in vivo experiments confirmed that miR-451a promoted the sensitivity of lung cancer cells-derived tumors to DOX treatment by reducing c-Myc. Therefore, our results revealed a new insight into DOX resistance of lung cancer cells and miR-451a could be considered as a potential therapeutic target to overcome drug resistance in lung cancer.
Subject(s)
DNA-Binding Proteins/metabolism , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , Epithelial-Mesenchymal Transition/drug effects , Lung Neoplasms/drug therapy , MicroRNAs/metabolism , Transcription Factors/metabolism , Animals , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice , Mice, Nude , MicroRNAs/genetics , Neoplasms, Experimental/drug therapy , Transcription Factors/geneticsABSTRACT
Clavicular fracture is a common upper limb fracture. Because of its special anatomical structure, it directly affects the function of the shoulder joint. The different injury mechanisms of clavicular fracture affect the mechanical effect of internal fixation, so the selection of internal fixation method has been puzzling orthopedists. As a modern computer based mechanical analysis, finite element analysis application in the internal fixation of clavicular fracture can not only clarify the pathogenesis of fractures, biomechanical properties of internal fixators and complications of fractures, but also provide guidance for preoperative planning. Therefore, it is beneficial to preoperative planning and individualized selection of surgical methods, and is expected to become an indispensable part in preoperative planning for clavicular fracture. In this paper, the pathogenesis, related influencing factors, selection of internal fixation and postoperative complications of clavicular fracture based on finite element analysis and problems during finite element analysis were reviewed.