Boo Lily, Ho Wan Yong, Mohd Ali Norlaily, Yeap Swee Keong, Ky Huynh, Chan Kok Gan, Yin Wai Fong, Satharasinghe Dilan Amila, Liew Woan Charn, Tan Sheau Wei, Cheong Soon Keng, Ong Han Kiat
Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras, Selangor, Malaysia.
Department of Biomedical Sciences, University of Nottingham, Semenyih, Selangor, Malaysia.
PeerJ. 2017 Jul 13;5:e3551. doi: 10.7717/peerj.3551. eCollection 2017.
Breast cancer spheroids have been widely used as models of cancer stem cells (CSCs), yet little is known about their phenotypic characteristics and microRNAs (miRNAs) expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.
乳腺癌球体已被广泛用作癌症干细胞(CSCs)模型,但对其表型特征和微小RNA(miRNAs)表达谱了解甚少。本研究的目的是评估富含MDA-MB-231球体的细胞的表型特征以了解其CSCs特性,并确定其miRNAs表达谱。与我们之前发表的MCF-7球体相似,MDA-MB-231球体也显示出典型的CSCs特征,即自我更新能力、假定的与CSCs相关的表面标志物的表达以及耐药性增强。从miRNA谱来看,miR-15b、miR-34a、miR-148a、miR-628和miR-196b在两种球体模型中均显示参与CSCs相关信号通路,这突出了这些miRNAs在维持CSCs特征中的作用。此外,在基底样球体中发现了独特的miRNA簇,即miR-205、miR-181a和miR-204,而在管腔样球体中鉴定出了miR-125、miR-760、miR-30c和miR-136。我们的结果突出了miRNAs的作用以及乳腺癌中富含球体的CSCs相关通路的新观点。