Abstract
IntroductionResistance of cancer stem/progenitor cells (CSPCs) to chemotherapy can lead to cancer relapse. Ovarian teratocarcinoma (OVTC) arises from germ cells and comprises pluripotent cells that can be used to study cancer cell stemness. In this study, we evaluated whether microRNA-21 (miR-21) promotes ovarian teratocarcinoma by maintaining cancer stem/progenitor populations.MethodsThe lentiviral delivery system was used to upregulate or to suppress the expression of miR-21 in the human ovarian teratocarcinoma cell line PA1 and cell growth assays were used to monitor the expression of miR-21 at different time points. Antibodies directed toward CD133, a stem cell marker, were used to identify CSPCs in the PA1 cell population, and the level of miR-21 expression was determined in enriched CSPCs. Stem cell functional assays (sphere assay and assays for CD133 expression) were used to assess the effects of miR-21 on progression of the CD133+ population.ResultsKnockdown of miR-21 in PA1 cells attenuated growth of PA1 cells whereas overexpression of miR-21 promoted cell growth. Moreover, knockdown of miR-21 resulted in a marked reduction in the CD133+ population and sphere formation of CSPCs. In contrast, overexpression of miR-21 resulted in a marked increase in the population of CD133+ cells as well as sphere formation of CSPCs.ConclusionsMicroRNA-21 plays a significant role in cancer growth by regulating stemness in cancer cells.
Highlights
Resistance of cancer stem/progenitor cells (CSPCs) to chemotherapy can lead to cancer relapse
Relative expression of miR-21 was detected with quantitative real-time polymerase chain reaction (PCR) and the relative amount of miR-21 is presented as the values of 2-ΔΔCt (A)
The results shown are from three reproducible experiments (C). * indicates significance at P values less than 0.05. miR, microRNA; OE: overexpression
Summary
Resistance of cancer stem/progenitor cells (CSPCs) to chemotherapy can lead to cancer relapse. Ovarian teratocarcinoma (OVTC) arises from germ cells and comprises pluripotent cells that can be used to study cancer cell stemness. We evaluated whether microRNA-21 (miR-21) promotes ovarian teratocarcinoma by maintaining cancer stem/progenitor populations. Studies have shown that miR-21 functions as an onco-miR by regulating tumorigensis and tumor progression [5,6,7] and has been found to be frequently up-regulated in cancer stem/progenitor. OVTC is caused by the abnormal development of pluripotent germ and embryonic cells, making it a good model for studying the behavior of CSPCs. CSPCs are thought to be a confounding factor for tumor recurrence and chemoresistance because of their capacity for unlimited self-renew and differentiation [19,26,27,28,29]. In addition to measuring CSPCs markers, tumor sphere formation is used to detect and enrich CSPCs [19,27]
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