mir-135b induces osteosarcoma invasion by the modulation of foxo-1 and c-myc

Background: osteosarcoma (os) is the most common type of bone malignancy. many studies have attempted to find the association between micrornas and cancer-associated processes. alterations in mirna expression through genetic or epigenetic changes, impairment of transcription factors, and ectopic expression of mirnas induce the development and progression of cancer. although mir-135b has been thoroughly documented as an oncogene in the majority of studies, some controversies remain about the conflicting role of mir-135b as a tumor-suppressor. objectives: the present study aimed at investigating the oncogenic and/or tumor-suppressing role of mir-135b in human os. methods: in this study, 21 os tissue samples, along with 21 adjacent bone tissues (normal) as control specimens were collected to analyze the expression of mir-135b. the saos2 cell-line was transiently transfected with the mir-135b mimic and inhibitor to assess its effect on two critical transcription factors, namely foxo-1 and c-myc. qrt-pcr was performed to quantify the expression of mir-135b in both os tissues and the saos2 cell-line. the mtt, cell migration, and cell invasion assays were used to characterize the mir-135b function. the western blot analysis was carried out to monitor the targets of mir-135b. finally, the changes in cellular functions such as migration and invasion, following the transfection of mir-135b mimic and inhibitor, were verified. results: the results showed that in comparison with the adjacent normal bone tissues, the expression of mir-135b was higher in os tissue samples, which inversely correlated with the expression rate of foxo-1, whereas the expression of c-myc had a direct relationship to mir-135b expression. functionally, the mir-135b mimic led to an increase in cell proliferation, invasion, and migration of os cancer cells. conclusions: mir-135b induces the proliferation and invasion of os cells by the degradation of foxo-1 and upregulation of c-myc.