MiR-129-5p inhibits non-small cell lung cancer cell stemness and chemoresistance through targeting DLK1

Journal Article · Sat Aug 19 04:00:00 EDT 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.06.041· OSTI ID:22719034

Ma, Zheng; Cai, Hongfei; Zhang, Yan; Chang, Liang; Cui, Youbin

Non-small cell lung cancer (NSCLC) stemness and chemoresistance represent significant barriers to successful treatment. Downregulation of microRNA 129 (miR-129) has been implicated in a variety of cancers, and miR-129-5p has recently been shown to reduce lung cancer proliferation and metastasis. In this study, we used NSCLC cell lines A549 and H460 to investigate the effects of miR-129-5p on NSCLC stemness and chemoresistance. CD133 + stem cells in both lines showed reduced miR-129-5p expression, and introducing miR-129-5p into these cells reduced stem cell markers and self-renewal ability, as measured by qRT-PCR, western blot, MTT assays, and sphere formation assays. MTT, colony formation, and DAPI staining assays further revealed that miR-129-5p inhibits NSCLC chemoresistance when the cells are treated with varying doses of CDDP. The target prediction algorithm TargetScan allowed us to identify notch signaling receptor delta-like 1 homolog (DLK1) as a potential target for miR-129-5p in its inhibition of NSCLC stemness and chemoresistance. Indeed, our DLK1 luciferase reporter plasmid demonstrated that miR-129-5p reduces DLK1 expression. Furthermore, DLK1 overexpression partially rescued inhibition of NSCLC stemness and chemoresistance caused by miR-129-5p. Overall, these results demonstrate that miR-129-5p inhibits NSCLC stemness and chemoresistance through direct targeting of DLK1. They suggest that miR-129-5p and DLK1 can play a role in an effective treatment strategy for NSCLC.

• OSTI ID: 22719034
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 490; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALGORITHMS
COLONY FORMATION
INHIBITION
LUCIFERASE
LUNGS
NEOPLASMS
PLASMIDS
PLATINUM COMPLEXES
POLYMERASE CHAIN REACTION
RECEPTORS
STEM CELLS