High expression of kinesin light chain-2, a novel target of miR-125b, is associated with poor clinical outcome of elderly non-small-cell lung cancer patients.

Abstract:

BACKGROUND:MiR-125b has critical role in non-small-cell lung cancer (NSCLC) cell migration, and its target genes have not been elucidated. Kinesin-1 light chain (KLC)-2 was predicted as one of miR-125b's targets by bioinformatics analysis. This study is to identify the function of KLC2 and its interaction with miR-125b in NSCLC. METHODS:Kinesin-1 light chain-2 protein expression and its clinical relevance were analysed in 140 matched NSCLC and adjacent non-neoplastic lung tissues. Both KLC2 gain- and loss-of-function analyses were performed in NSCLC cell lines by transient transfection. The direct interaction between KLC2 and miR-125b was confirmed by a luciferase reporter assay and a transient co-transfection assay as well as an analysis of eight matched clinical samples. RESULTS:KLC2 protein was upregulated in NSCLC cell lines and tissues, and was an independent predictor of poor prognosis for elderly NSCLC patients. Kinesin-1 light chain-2 remarkably enhanced the invasive and migratory ability of NSCLC cells. MiR-125b inhibited KLC2 3'-untranslated region luciferase activity and protein expression, and inversely correlated with KLC2 expression in clinical samples. Kinesin-1 light chain-2 almost completely reversed miR-125b-induced inhibition on migration and invasion. CONCLUSIONS:Kinesin-1 light chain-2 protein overexpression predicts poor survival in elderly NSCLC patients. Kinesin-1 light chain-2 acts as a proto-oncogene and a functional target of miR-125b in NSCLC cells.

journal_name

Br J Cancer

authors

Wang M,Zhu X,Sha Z,Li N,Li D,Chen L

doi

10.1038/bjc.2015.3

subject

Has Abstract

pub_date

2015-03-03 00:00:00

pages

874-82

issue

5

eissn

0007-0920

issn

1532-1827

pii

bjc20153

journal_volume

112

pub_type

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