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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Cancer 1/2018

MiR-199a/b-3p inhibits gastric cancer cell proliferation via down-regulating PAK4/MEK/ERK signaling pathway

Zeitschrift:
BMC Cancer > Ausgabe 1/2018
Autoren:
Bin Zeng, Wei Shi, Gao Tan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12885-017-3949-2) contains supplementary material, which is available to authorized users.

Abstract

Background

Gastric cancer (GC) is one of the most frequent malignant tumors and the molecular mechanism underlying its proliferation remains far from completely understood. Although accumulating evidence shows that abnormal expression of microRNA (miRNA) is involved in tumorigenesis, the role of specific miRNAs involved in GC remains elusive. MiR-199a/b-3p functions as a tumor suppressor in diverse cancers, but its expression, function, and mechanism in GC remain unclear. Our aim is to explore miR-199a/b-3p expression and its role in regulating GC cell proliferation.

Methods

Real-time PCR was performed to determine miR-199a/b-3p expression in GC tissues and normal adjacent tissues as well as normal gastric mucosal cell line GES-1 and GC cell lines MGC-803 and SGC-7901. MTT assay and Western blot were performed to determine cell proliferation and expression of PAK4, p-MEK and p-ERK, respectively. MiR-199a/b-3p mimics-transfected assay and PAK-specific siRNA assay were performed to determine their function in cell proliferation, respectively. GC xenograft nude mice were used to determine miR-199a/b-3p function in cell proliferation.

Results

MiR-199a/b-3p expression was significantly decreased in GC tissues and GC cell lines MGC-803 and SGC-7901. MiR-199a/b-3p over-expression and PAK4 silencing inhibited cell proliferation and diminished the activation of p-MEK and p-ERK in MGC-803 and SGC-7901 cells, and miR-199a/b-3p over-expression reduced PAK4 expression. MiR-199a/b-3p over-expression suppressed MGC-803 cell growth and PAK4 expression in nude mice.

Conclusions

miR-199a/b-3p inhibits GC cell proliferation via down-regulating PAK4/MEK/ERK signaling pathway and may be a novel prognostic biomarker and a potential therapeutic target for GC patients.
Zusatzmaterial
Additional file 1: Figure S1. Enrichment analysis of predicted miR-199a/b-3p targets in GCBI pathway database; Figure S2. MiR-199a/b-3p over-expression and PAK4 knockdown inhibited the cell proliferation ability of GC cell line 7901 in vitro as analyzed by CCK-8 assay; Table S1. The association of miR-199a/b-3p relative expression with the clinic-pathological characteristics in 20 GC patients; Table S2. Primers used in this study; Table S3. TargetScan prediction of miR-199a/b-3p target sites in PAK4; Table S4. Sequences of miR-199a/b-5p and miR-199a/b-3p; Table S5. Top 25 predicted targets of miR-199-3p/5p sorted by aggregate PCT (DOCX 535 kb)
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Literatur
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