Long noncoding RNA HOXD-AS1 promotes non-small cell lung cancer migration and invasion through regulating miR-133b/MMP9 axis

Publication date: October 2018
Source:Biomedicine & Pharmacotherapy, Volume 106
Author(s): Huan Xia, Hongyu Jing, Yang Li, Xiaohong Lv
HOXD antisense growth associated long noncoding RNA (HOXD-AS1) was reported to be dysregulated and exert crucial roles in tumorigenesis and progression of multiple malignancies. However, the role and mechanism of action of HOXD-AS1 in the carcinogenesis and progression of non-small lung cell cancers (NSCLC) remains largely unknown. HOXD-AS1, miR-133a and Matrix metallopeptidase 9 (MMP-9) mRNA expression were detected by quantitative real-time polymerase chain reaction assays in NSCLC tissues and cell lines. Cell counting kit-8, wound healing and transwell invasion assays were performed to evaluate cell proliferation, migration and invasion abilities, respectively. Luciferase assays were used to investigate binding seeds between miR-133b and HOXD-AS1. Western blot assay were performed to detect protein expression. Here higher expression of HOXD-AS1 was found in NSCLC tumor tissues compared with normal lung tissues, and was associated with lymph node metastasis, high tumor node metastasis (TNM) stage, and poor overall survival rate of patients with NSCLC. Knockdown of HOXD-AS1 significantly inhibited proliferation, migration and invasion of NSCLC cells. Additionally, we found that miR-133b was a direct downstream target of HOXD-AS1 in NSCLC. miR-133b inhibition reverse the inhibitory effect of HOXD-AS1 knockdown on the proliferation, migration, and invasion of NSCLC cells. Furthermore, HOXD-AS1 positively regulated the expression of MMP-9 (a target of miR-133b) in NSCLC cells. These results suggest that HOXD-AS1 might be a potential prognostic biomarker and a novel therapeutic target for treating NSCLC.



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