Aims: MiR-135b is a downstream effector of oncogenic signaling pathways. This study aimed to reveal the underlying regulation and significance of miR-135b in gastric cancer.
Materials and methods: The influence of Wnt and PI3K/AKT signaling pathways on the transcriptional activation of the miR-135b promoter was determined by dual-luciferase reporter assays. In vitro experiments, including the cell counting kit-8 (CCK8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry analysis and malignant phenotype profiles, were conducted to determine the oncogenic role of miR-135b in gastric cancer. To analyze the clinical significance of miR-135b in gastric cancer, the expression profile of miR-135b in tissue specimens and plasma was examined by quantitative real-time PCR (qRT-PCR).
Key findings: Oncogenic signaling pathways represented by Wnt and PI3K/AKT promoted the transcriptional activation of the miR-135b promoter in gastric cancer. Downregulation of miR-135b inhibited proliferation, promoted apoptosis, and suppressed the migratory, invasive, and adherent abilities as well as the cancer stem cell phenotype of gastric cancer cells. High expression of miR-135b in gastric cancer tissues was tightly associated with poor prognosis and malignant transformation represented by metastasis of gastric cancer. The miR-135b level in the plasma of gastric cancer patients was significantly higher than that in healthy individuals.
Significance: MiR-135b is a potential downstream effector of the Wnt and PI3K/AKT signaling pathways in gastric cancer. High expression of miR-135b may predict malignant transformation and poor prognosis of gastric cancer. This study reveals the potential role of miR-135b as a target for the early diagnosis and therapy of gastric cancer.
Keywords: Cancer metastasis; Early diagnosis; Gastric cancer; Malignant transformation; MiR-135b; Poor prognosis.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.