MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells

Abstract

Osteosarcoma is the most common primary bone tumor and poor prognosis for osteosarcoma patients is mainly due to chemotherapy resistance. MicroRNAs are important to maintain pathophysiological mechanisms of cancer and influence cell sensitivity to chemotherapy. In this study, we tested the functions of microRNA-21 for malignant features as well as for drug resistance of osteosarcoma. We used Northern blot to measure microRNA-21 levels in osteosarcoma-derived cell lines. MicroRNA-21 activity was modulated by either expressing a sponge to decrease its activity in an osteosarcoma-derived cell line expressing high levels of microRNA-21 or by introducing pri-microRNA-21 in a cell line with low endogenous levels. Cell migration was determined in a scratch assay and cell proliferation was measured by performing growth curve analysis. Sensitivity of the cells towards chemotherapeutics was investigated by performing cell viability assays and calculating the IC50 values. While cell migration was unaffected by modulated microRNA-21 levels, microRNA-21 inhibition slowed proliferation and exogenously expressed microRNA-21 promoted this process. Modulated microRNA-21 activity failed to effect sensitivity of osteosarcoma-derived cell lines to doxorubicin or methotrexate. Contrarily, reduction of microRNA-21 activity resulted in enhanced resistance towards cisplatin while ectopic expression of microRNA-21 showed the opposite effect. Increased microRNA-21 levels repressed the expression of Sprouty2 and ectopic expression of Sprouty2 was able to largely rescue the observed effects of microRNA-21 in osteosarcoma. In summary, our data indicate that in osteosarcoma microRNA-21 expression is an important component for regulation of cell proliferation and for determining sensitivity to cisplatin.

Circular RNA circHIAT1 inhibits proliferation and epithelial‐mesenchymal transition of gastric cancer cell lines through downregulation of miR‐21

“…PTEN, an anticancer factor, is inactivated by miR‐21 in the development of GC. [ 41 ] Similarly, our results also showed that the level of PTEN was reduced after transfection with miR‐21 mimic. For the first time, we showed the regulatory relationship between circHIAT1, miR‐21, and PTEN/PI3K/AKT and ERK.…”

MicroRNA-765 Enhances the Anti-Angiogenic Effect of CDDP via APE1 in Osteosarcoma

“…Thus, in this study, we investigated the impact of miR-765 on the anti-angiogenic effect of cisplatin. Several studies have shown the impact of miR-21 on sensitivity of osteosarcoma-derived cells towards chemotherapies 18 . MicroRNAs are critical oncomiRs in tumorigenesis, and their expression has been shown to be up-regulated in breast carcinoma 19 .…”

Common Chemical Inductors of Replication Stress: Focus on Cell‐Based Studies

“…miR-378 was shown to reverse resistance to cisPt in lung adenocarcinoma cells [134], whereas miR-27a was shown to be upregulated in a multidrug resistant ovarian cancer cell line, contributing to cisPt resistance [135]. miR-21 increases the cisPt sensitivity of osteosarcoma-derived cells [136]. For references to particular studies using cisPt, refer to Table 1.…”