The Tumor-Suppressive MicroRNA-135b Targets c-Myc in Osteoscarcoma

Abstract

Osteosarcoma is the most common primary tumor of the bone. It leads to many deaths because of its rapid proliferation and metastasis. Recent studies have shown that microRNAs are important gene regulators that are involved in various cancer-related processes. In this study, we found that miR-135b was down-regulated in both osteoscarcoma patient tumor tissues and osteoscarcoma cell lines in comparison to paired adjacent non-tumor bone tissue. We observed that a lower level of miR-135b was associated with metastasis. The ectopic expression of miR-135b markedly suppressed osteoscarcoma cell proliferation, migration, and invasion. Conversely, the inhibition of miR-135b expression dramatically accelerated cell proliferation, migration, and invasion. The forced expression of miR-135b in osteosarcoma cells resulted in a significant reduction in the protein level of c-Myc and repressed the activity of a luciferase reporter that contained the 3′-untranslated region of the c-Myc mRNA. These effects were abolished by the mutation of the predicted miR-135b-binding site, which indicates that c-Myc may be a miR-135b target gene. Moreover, the ectopic expression of c-Myc partially reversed the inhibition of cell proliferation and invasion that was caused by miR-135b. These data therefore suggest that miR-135b may function as a tumor suppressor to regulate osteosarcoma cell proliferation and invasion through a mechanism that targets the c-Myc oncogene. These findings indicate that miR-135b may play a role in the pathogenesis of osteosarcoma.

Perturbation of IGF2BP1 Transcriptome upon the Interplay between miR-486-5p and let-7a

“…Loss and gain of function experiments for miR-486-5p in Huh-7 cells repressed the expression of c-MYC on the protein level, which supports previous findings where c-MYC expression was manipulated by miRNAs like miR-135b and miR-181a [21].Then the impact on let-7a via c-MYC was investigated through intended over expression of miR-486-5p in Huh-7 cells compared to the mockuntransfected cells, forced expression of miR-486-5p resulted in a significant up-regulation of let-7a in Huh-7 cells. This goes along with the idea that repressing c-MYC relives let-7a from its inhibitory effect.…”

Plant flavonoid taxifolin inhibits the growth, migration and invasion of human osteosarcoma cells

“…It is a multi-functional proto-oncogene and a nuclear phosphoprotein that mediates cell proliferation, cell cycle arrest and apoptosis (24). Abnormal c-myc mRNA expression promotes the invasion of osteosarcoma cells (25) and leads to cancer development (26,27), whereas c-myc protein attenuation leads to diminished cell proliferation and tumor growth in osteosarcoma (28). Abnormal c-myc function has been identified in stomach, breast, colon and lung cancers (29).…”

miR-451 suppresses bladder cancer cell migration and invasion via directly targeting c-Myc

“…It has been reported that altered expression of c-Myc is induced by upstream signal pathways (33). In addition, various studies found miRNAs may be upstream regulators of c-Myc by targeting its mRNA, then inhibiting its translation (34,35). In addition, miRNA has been proved to be able to regulate chemoresistance of cancer cells by inhibiting c-Myc (36,37).…”