Upregulation of miRNA‑301a‑3p promotes tumor progression in gastric cancer by suppressing NKRF and activating NF‑κB signaling

Xu,Xiaodong; Xia,Yingjie; Ma,Jie; Li,Weijun; Niu,Nan; Li,Xiao; Tao,Houquan; Xu,Ji; He,Xujun

doi:10.3892/ijo.2020.5072

Upregulation of miRNA‑301a‑3p promotes tumor progression in gastric cancer by suppressing NKRF and activating NF‑κB signaling

Authors:
- Xiaodong Xu
- Yingjie Xia
- Jie Ma
- Weijun Li
- Nan Niu
- Xiao Li
- Houquan Tao
- Ji Xu
- Xujun He
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Affiliations: Department of Surgical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of General Surgery, People's Hospital of Xianju, Taizhou, Zhejiang 317300, P.R. China
Published online on: May 26, 2020 https://doi.org/10.3892/ijo.2020.5072
Pages: 522-532
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNA‑301a (miRNA/miR‑301a) and nuclear factor (NF)‑κB signaling play important roles in tumor invasion, migration and progression. However, the role of miRNA‑301a‑3p in human gastric cancer (GC), and specifically in the activation of NF‑κB signaling, remains unclear. The aim of the present study was to investigate miRNA‑301a‑3p expression in GC progression and the molecular mechanisms as regards the regulation of NF‑κB signaling. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect miRNA‑301a‑3p expression in GC and paired normal tissues. The association between the expression of miRNA‑301a‑3p and patient pathological parameters and the prognosis of GC was statistically analyzed using an in situ hybridization (ISH) assay. An MTS assay and a Transwell assay were performed to evaluate the effects of miRNA‑301a‑3p on the proliferation, invasion and migration of GC cells. RT‑qPCR and western blot analysis were used to analyze the association between miRNA‑301a‑3p and nuclear factor‑κB repressing factor (NKRF) expression and the corresponding downstream NF‑κB signaling molecules. A luciferase assay was used to verify the target effect of miRNA‑301a‑3p and NKRF. It was found that miRNA‑301a‑3p expression was significantly higher in 30 cases of primary GC compared with matched normal tissues. Additionally, the ISH assay indicated that the high expression of miRNA‑301a‑3p in GC was associated with tumor invasion depth, lymph node metastasis, lymph node invasion and tumor metastasis stage. Patients whose tumors had a higher miRNA‑301a‑3p expression level exhibited a poorer prognosis. The in vitro assay indicated that miRNA‑301a‑3p affected the proliferative and invasive ability of GC cells by targeting the expression of NKRF, which then affected NF‑κB signaling. Therefore, it was hypothesize that miRNA‑301a‑3p promotes GC progression and affects the prognosis of patients with GC by targeting NKRF, which in turn, directly influences NF‑κB activation.

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