Direct targeting of MAPK8IP1 by miR-10a-5p is a major mechanism for gastric cancer metastasis

Oncol Lett. 2017 Mar;13(3):1131-1136. doi: 10.3892/ol.2016.5544. Epub 2016 Dec 28.

Abstract

MicroRNA (miRNA) are endogenous non-coding RNAs that suppress gene expression at the transcriptional, post-transcriptional or translational level by targeting the 3'-UTRs of specific mRNAs. miR-10a has been frequently reported to be aberrantly overexpressed in human tumors. In gastric cancer (GC), miR-10a has an important role in the metastasis from primary GC to lymph nodes. However, the role and relevant pathways of miR-10a in GC metastasis remain largely unknown. The present study was performed using 41 GC and 20 normal gastric mucosa tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that MAPK8IP1 was significant downregulated in GC tissue. A statistically significant inverse correlation was detected between miR-10a and MAPK8IP1 mRNA expression levels in GC specimens. Luciferase reporter assay and qPCR results suggested that MAPK8IP1 was a direct target of miR-10a in GC cells. Matrigel invasion assay and wound-healing assay results showed that MAPK8IP1 overexpression rescued the increased migration ability of miR-10a effectors in MKN45 cells. Furthermore, the underlying mechanism of miR-10a functions in GC was explored. The findings indicated that miR-10a-5p directly targets MAPK8IP1, as a major mechanism for gastric cancer metastasis. The results of the present study suggested that miR-10a may be a potential target for the treatment of GC in the future.

Keywords: gastric cancer; metastasis; miR-10a-5p; mitogen-activated protein kinase 8IP1; mitogen-activated protein kinase signaling.