微小RNA-21通过在体外维持癌症干细胞/祖细胞群体来促进卵巢畸胎瘤PA1细胞系的生长。

INTRODUCTION

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. In this study, we evaluated whether microRNA-21 (miR-21) promotes ovarian teratocarcinoma by maintaining cancer stem/progenitor populations.

METHODS

The 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.

RESULTS

Knockdown 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.

CONCLUSIONS

MicroRNA-21 plays a significant role in cancer growth by regulating stemness in cancer cells.

引言

癌症干细胞/祖细胞（CSPCs）对化疗的耐药性可导致癌症复发。卵巢畸胎癌（OVTC）起源于生殖细胞，包含可用于研究癌细胞干性的多能细胞。在本研究中，我们评估了微小RNA-21（miR-21）是否通过维持癌症干细胞/祖细胞群体来促进卵巢畸胎癌。

方法

使用慢病毒递送系统上调或抑制人卵巢畸胎癌细胞系PA1中miR-21的表达，并使用细胞生长测定法监测不同时间点miR-21的表达。针对干细胞标志物CD133的抗体用于鉴定PA1细胞群体中的CSPCs，并在富集的CSPCs中测定miR-21的表达水平。使用干细胞功能测定法（球体测定法和CD133表达测定法）评估miR-21对CD133+群体进展的影响。