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Abstract: Metastatic relapse, development of drug resistance in cancer cells and adverse side effects of chemotherapeutic agents are the major obstacles for effective chemotherapy against triple-negative breast cancer. To address these problems, miR-34a, a potent endogenous tumor suppressive molecule in breast cancer, was co-encapsulated with doxorubicin (DOX) into hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs) and simultaneously delivered into breast cancer cells for improved therapeutic effects of drug. DOX-miR-34a co-loaded HA-CS NPs were successfully prepared through ionotropic gelation method in water. In vitro and in vivo experiments showed that miR-34a and DOX can be efficiently encapsulated into HA-CS NPs and delivered into tumor cells or tumor tissues and enhance anti-tumor effects of DOX by suppressing the expression of non-pump resistance and anti-apoptosis proto-oncogene Bcl-2. In addition, intracellular restoration of miR-34a inhibited breast cancer cell migration via targeting Notch-1 signaling. The obtained data suggest that co-delivery of DOX and miR-34a could achieve synergistic effects on tumor suppression and nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy. [Copyright &y& Elsevier]

Abstract: The expression of miR-203 has been reported to be significantly down-regulated in esophageal cancer. We showed here that overexpression of miR-203 in esophageal cancer cells dramatically increased cell apoptosis and inhibited cell proliferation, migration and invasion as well as tumor growth and down-regulated miR-21 expression. We subsequently identified that small GTPase Ran was a target gene of miR-203. Furthermore, Ran restoration partially counteracted the tumor suppressive effects of miR-203 and increased miR-21 expression. Taken together, our findings suggest that miR-203 may act as novel tumor suppressor in esophageal cancer through down-regulating the expression of Ran and miR-21. [Copyright &y& Elsevier]