Non-coding RNAs and exosomal ncRNAs in multiple myeloma: An emphasis on molecular pathways.

One of the most common hematological malignancies is multiple myeloma (MM) that its mortality and morbidity have increased. The incidence rate of MM is suggested to be higher in Europe and various kinds of therapeutic strategies including stem cell transplantation. However, MM treatment is still challenging and gene therapy has been shown to be promising. The non-coding RNAs (ncRNAs) including miRNAs, lncRNAs and circRNAs are considered as key players in initiation, development and progression of MM. In the present review, the role of ncRNAs in MM progression and drug resistance is highlighted to provide new insights for future experiments for their targeting and treatment of MM. The miRNAs affect proliferation and invasion of MM cells, and targeting tumor-promoting miRNAs can induce apoptosis and cell cycle arrest, and reduces proliferation of MM cells. Furthermore, miRNA regulation is of importance for modulating metastasis and chemotherapy response of tumor cells. The lncRNAs exert the same function and determine proliferation, migration and therapy response of MM cells. Notably, lncRNAs mainly target miRNAs in regulating MM progression. The circRNAs also target different molecular pathways in regulating MM malignancy that miRNAs are the most well-known ones. Furthermore, clinical application of ncRNAs in MM is discussed.

Design of Anti-Angiogenic Peptidomimetics and Evaluation their Biological Activity by In Vitro Assays.

BACKGROUND: One of the important therapeutic approaches in cancer field is development of compounds which can block the initial tumor growth and the progression of tumor metastasis with no side effects. Thus, the recent study was carried out to design anti-VEGFR2-peptidomimetics as the most significant factor of angiogenesis process- and evaluate their biological activity by in vitro assays. METHODS: We designed anti-VEGFR2 peptidomimetics with anti-angiogenic activity, including compound P (lactam derivative) and compound T (indole derivative) by using in silico methods. Then, the inhibitory activity on angiogenesis was evaluated by using angiogenesis specific assays such as Human Umbilical Vein Endothelial Cell (HUVEC) proliferation, tube formation in Matrigel, MTT and Real-Time PCR. IC50 values of the compounds were also determined by cytotoxicity plot in MTT assay. RESULTS: Compounds P and T inhibited HUVEC cell proliferation and viability in a dose-dependent manner. The IC50 for compound T and compound P in HUVEC cell line were 113 and 115 µg/ml, respectively. Tube formation assay revealed that both compounds can inhibit angiogenesis effectively. The results of Real-Time PCR also showed these compounds are able to inhibit the expression of CD31 gene in HUVEC cell line. CONCLUSION: Our study suggested that compounds P and T may act as therapeutic molecules, or lead compounds for development of angiogenesis inhibitors in VEGF-related diseases.