Promoter methylation of MIR34a and MIR34b/c occurs frequently and concomitantly in breast and lung cancer, as well as in pulmonary diseases tissues, but not in breast normal tissues adjacent to tumor.
In vivo tumor targeting and therapy was investigated in an orthotopic lung cancer model by microCT, fluorescence imaging, and immunohistochemistry.<b>Results:</b> The singular nanoscale formulation, incorporating oncogene siKRAS, tumor-suppressor stimulating miR-34a, and cisplatin, has shown enhanced toxicity against lung cancer cell line, KP cell.
Collectively, these results demonstrate a previously unrecognized role for miR-34a in modulating IR-induced senescence in human NSCLC cells and suggest that pharmacological intervention of miR-34a expression may represent a new therapeutic strategy for improving the efficacy of lung cancer radiotherapy.
Herein, we reveal that miR-34a is significantly downregulated in NSCLC tissues and cell lines, suggesting that miR-34a might function as a tumor suppressor in lung cancer.
To explore new therapeutic options, we successfully encapsulated MicroRNA-34a (miR-34a), a potent endogenous tumor suppressor in NSCLC into S6 aptamer-conjugated dendrimer to form lung cancer-targeted gene delivery nanoparticles (PAM-Ap/pMiR-34a NPs).
The therapeutic potential of microRNAs for preventing and treating lung cancer using the Kras(LSL-G12D/+);p53(LSL-R172H/+)mouse model suggests that miR-34 may be useful in sensitizing tumors to other conventional therapeutics.
Moreover, we demonstrated that pretransfection of miR-34a could increase the sensitivity of both lung cancer cell lines to cisplatin (DDP), and this could be reverted by the miR-34a inhibitor.
These findings demonstrate that ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression and provide a compelling rationale to develop miR-34a as a therapeutic agent in lung cancer patients.
Recently, miR-34 family has been shown to be part of the p53 pathway which is frequently involved in lung cancer, and the expression of miR-34 has been reported to be regulated by DNA methylation.
Therapeutic delivery was demonstrated using mimics of the tumor suppressors, microRNA-34a (miR-34a) and let-7, both of which are often down regulated or lost in lung cancer.