Yuanyuan Wu1, Gui Hu2, Runliu Wu3, Ni Gong4. 1. Department of Hepatobiliary Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China. 2. Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China. 3. Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China. 4. Department of Nursing, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China. Electronic address: 13787796333@163.com.
Abstract
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.
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 cancerpatients 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.
Authors: Gleb O Skryabin; Svetlana V Vinokurova; Sergey A Galetsky; Danila S Elkin; Alexey M Senkovenko; Darya A Denisova; Andrey V Komelkov; Ivan S Stilidi; Ivan N Peregorodiev; Olga A Malikhova; Oiatiddin T Imaraliev; Adel D Enikeev; Elena M Tchevkina Journal: Cancers (Basel) Date: 2022-07-07 Impact factor: 6.575