MiRNA-20A Upregulates TAK1 and Increases Proliferation in Osteosarcoma Cells

Abstract

Aim:The aim of this study is to explore the function of miR-20a in osteosarcoma. Materials & methods: miR-20a expression was measured by real-time PCR. miR-20a mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to observe effects on colony formation and tumor growth. Moreover, relationships of miR-20a with TAK1 were investigated by western blot and luciferase activity. Results: We found that miR-20a was downregulated in osteosarcoma, and overexpression of miR-20a reduced colony formation and tumor growth. Furthermore, the data revealed that the function of miR-20a was probably exerted via targeting the TAK1 expression. Overexpression of miR-20a sensitizes the osteosarcoma cells to chemotherapeutic drugs. Conclusion: Our data identify the role of miR-20a in osteosarcoma growth, indicating its potential application in chemotherapy. Osteosarcoma is the most common primary malignant bone tumor with high morbidity in young adults and children, comprising 2.4% of all malignancies in pediatric patients and about 20% of all primary bone tumors [1]. It occurs mainly around regions with active bone growth and reparation. Osteosarcoma is highly aggressive and responded poorly to chemotherapy, and the 5-year survival rate for patients with metastatic osteosarcoma is only 14% [2]. Therefore, it is of extreme significance to elucidate novel molecular targets to develop alternative therapeutic target for this disease.miRNAs are a small family of noncoding RNAs that play important roles in the development of human diseases by negatively regulating gene expression at either post-transcriptional or translational levels [3,4]. Over the last decade, many miRNAs have been showed in regulating diverse biological events such as cell proliferation, differentiation and apoptotic processes [5][6][7], which are important in the development of cancer. Accumulated evidence indicated that aberrant expression of miRNAs associates with various types of cancer. These dysregulated miRNAs function as either oncogenes or tumor suppressors in carcinogenesis and progression of cancers [8,9]. Thus, to explore the aberrant miRNAs expression in osteosarcoma might lead to the discovery of novel miRNAs biomarkers.In this study, we found that miR-20a was downregulated in osteosarcoma samples and osteosarcoma cell lines, and the ectopic expression of miR-20a reduced cell colony formation in vitro and tumor growth in vivo. Furthermore, bioinformatic prediction and experimental validation revealed that the function of miR-20a was probably exerted via targeting the TAK1 expression. To translate these findings, overexpression of miR-20a sensitizes the osteosarcoma cells to chemotherapeutic drugs. Collectively, our data identify the key role of miR-20a in osteosarcoma growth, indicating its potential application in cancer chemotherapy.

TAK1 regulates endothelial cell necroptosis and tumor metastasis

“…The factors responsible for the development of such premetastatic niches are believed to be directly secreted into the circulation by cells of the primary tumor or to be transported via tumor-shed extracellular vesicles or exosomes and include inflammatory cytokines and chemokines, hormones, proangiogenic factors, extracellular matrix components, metabolites and lipids, as well as genetic material, including DNA, mRNA, and miRNA [19,24]. Among these, miRNAs were shown to alter TAK1 expression levels [25][26][27][28], to regulate b, d, g) from biological sextuplicates (n = 6) (a-d) or from n = 4-6 animals per condition (f, g). *P < 0.05; **P < 0.01; ***P < 0.001.…”

GLUT1 regulates cell glycolysis and proliferation in prostate cancer

“…The expression of GLUT1 is regulated by many factors, such as serine/threonine kinase Akt1 and PI3 signaling, with the most important factor being hypoxia and the transcription factor hypoxia‐inducible factor 1 (HIF‐1) . Studies focused on the function of GLUT1 in tumors showed that GLUT1 promotes proliferation and metastasis and inhibits apoptosis in several cancer types, such as lung cancer and breast cancer . Nevertheless, the expression and function of GLUT1 in PCa cell lines have yet to be clarified.…”

Ailanthone: A novel potential drug for treating human cancer (Review)

“…It is the most common adult acute leukemia and accounts for ~80% of cases ( 52 ). microRNAs (miRNAs/miRs) are short RNA molecules that negatively regulate gene expression; miRNAs are downregulated in numerous types of solid tumors, such as gastric cancer ( 53 ), lung cancer ( 54 ) and osteosarcoma ( 55 ). Moreover, abnormal expression levels of miRNAs (miR-128a, miR-92a, miR-143 and miR-342) are associated with the development of AML ( 56 , 57 ).…”