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MicroRNA‑18b acts as an oncogene in gastric cancer by directly targeting Kruppel‑like factor 6.

Mol Med Rep. 2019 Mar;19(3):1926-1934. doi:10.3892/mmr.2019.9830. Epub 2019 Jan 08
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摘要


Gastric cancer (GC) is the fourth most frequently occurring cancer and the second most common cause of cancer‑associated mortality worldwide. An increasing number of studies have reported that microRNAs (miRNAs/miRs) contribute to the regulation of GC development and progression. Therefore, investigation of the miRNAs involved in the development of GC may result in identification of an effective therapeutic target for patients with this malignancy. miR‑18b has been reported to be aberrantly expressed in several types of human cancer. However, the expression pattern, biological role and specific functional mechanism of miR‑18b in GC remains to be elucidated. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis revealed that miR‑18b was significantly upregulated in GC tissues and cell lines compared with normal gastric tissues and the human gastric epithelial immortalized cell line GES‑1, respectively. High miR‑18b expression was significantly associated with lymph node metastasis, invasive depth and the Tumor Node Metastasis stage of patients with GC. Additionally, functional assays indicated that the inhibition of miR‑18b attenuated cell proliferation and invasion in GC. Furthermore, Kruppel‑like factor (KLF)‑6 was identified as a direct target gene of miR‑18b in GC, from the results of bioinformatics analysis, a luciferase reporter assay, RT‑qPCR and western blot analysis. An inverse association was observed between miR‑18b and KLF6 mRNA levels in GC tissues. KLF6 knockdown partially abrogated the effects of miR‑18b inhibition on GC cell proliferation and invasion. Therefore, miR‑18b/KLF6 targeted therapy may provide a promising treatment for patients with GC.

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