Busulfan inhibits growth of human osteosarcoma through miR‐200 family microRNAs in vitro and in vivo

Abstract

Osteosarcoma typically arises in tissues of mesenchymal origin, and is the most malignant bone tumor characterized by high local aggressiveness, with poor therapeutic outcome. Busulfan has been widely used to treat CML. So far, there are no reports on the therapeutic effect of busulfan on osteosarcoma. Here, we showed that busulfan dose-dependently reduced the cell viability and proliferation, and induced cell apoptosis, senescence, and reactive oxygen species levels in two osteosarcoma cell lines. Moreover, a series of loss-of-function and gain-of-function experiments further indicated that busulfan may have its anti-osteosarcoma effect by upregulating the microRNA-200 (miR-200) family which subsequently downregulated its target genes ZEB1 and ZEB2. Furthermore, treatment with busulfan potentially inhibited the growth of implanted osteosarcoma in nude mice. Taken together, our data suggest that busulfan may have an anti-osteosarcoma effect through downregulating ZEB1 and ZEB2 through activating the miR-200 family, highlighting a possibility of using busulfan as a novel therapy for osteosarcoma.

miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD

“…This results in mRNA degradation or inhibition of post-transcriptional translation, thereby altering processes related to the cell cycle, apoptosis, cell proliferation and cell migration (19). miRNA-130b is located on chromosome 22 and the mature sequence is 22 nucleotides in length.…”

miR-574-3p acts as a tumor promoter in osteosarcoma by targeting SMAD4 signaling pathway

“…Discussion miR-574 has been found to be upregulated in several types of cancers, including lung cancer, bladder cancer and prostate cancer (11)(12)(13)19). Foss et al (17) also suggested miR-574 as a serum biomarker of non-small cell lung cancer.…”

“…All diagnoses were based on pathological and/or cytological evidence (10). The histological features of the specimens were evaluated by senior pathologists according to the World Health Organization classification criteria (11)(12)(13). Tissues were obtained prior to chemotherapy and radiotherapy, and were immediately frozen and stored at -80˚C prior to reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assay (3,5,10).…”

“…The critical functions of numerous miRNAs in cancer biology have been illustrated, including the regulation of various cellular processes, such as proliferation and apoptosis (3,5,9,10). The abnormality of miR-574-3p was observed in patients with non-small cell lung cancer and prostate cancer, and it was found that this miRNA regulated colorectal cancer growth and plays important roles in bladder cancer cell lines (11)(12)(13). Nevertheless, whether miR-574-3p participates in the progression of osteosarcoma remains unclear.…”

miR-133 inhibits pituitary tumor cell migration and invasion via down-regulating FOXC1 expression

“…One of these miRs, miR-133, has been shown to play a role in tumor suppression in a variety of cancers, including inhibiting breast cancer cell migration and invasion, gastric cancer cell growth and migration, and liver fibrosis (Esquela- Kerscher and Slack, 2006;Cheng et al, 2012;Liu et al, 2014;Mei et al, 2014;Wang et al, 2014;Yongchun et al, 2014;Xie et al, 2015;Zhang et al, 2015). Recent studies have shown that miRs may be a new regulatory mechanism involved in the onset of pituitary adenoma, providing a new method for the diagnosis and treatment of pituitary adenoma (Trivellin et al, 2012;Gadelha et al, 2013;Di Ieva et al, 2014;Leone et al, 2014).…”