miR‑146a‑5p targets TCSF and influences cell growth and apoptosis to repress NSCLC progression

Huang,Wen‑Ting; He,Rong‑Quan; Li,Xiao‑Jiao; Ma,Jie; Peng,Zhi‑Gang; Zhong,Jin‑Cai; Hu,Xiao‑Hua; Chen,Gang

doi:10.3892/or.2019.7030

miR‑146a‑5p targets TCSF and influences cell growth and apoptosis to repress NSCLC progression

Authors:
- Wen‑Ting Huang
- Rong‑Quan He
- Xiao‑Jiao Li
- Jie Ma
- Zhi‑Gang Peng
- Jin‑Cai Zhong
- Xiao‑Hua Hu
- Gang Chen
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Affiliations: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China, Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China, Department of PET‑CT, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China, Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China, Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
Published online on: February 25, 2019 https://doi.org/10.3892/or.2019.7030
Pages: 2226-2240
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Several studies have indicated that microRNAs (miRs) mediate multiple pathways associated with tumorigenesis and progression. Our preliminary study experimentally verified that miR‑146a‑5p has a role in the biological behavior of non‑small cell lung cancer (NSCLC) cells. To perform further investigation of miR‑146a‑5p, the present study evaluated miR‑146a‑5p by targeting its downstream gene tumor collagenase stimulatory factor (TCSF) to influence cell viability, proliferation and apoptosis in NSCLC. Online sequence prediction, a thorough search of the open source database The Cancer Genome Atlas (TCGA), immunohistochemistry (IHC) of TCSF in clinical lung cancer tissues, and a dual‑luciferase assay, as well as assays to test viability, proliferation and apoptosis in vitro, were conducted to explain the targeted regulation association between miR‑146a‑5p and TCSF in NSCLC. The miRanda and TargetScanHuman database revealed that TCSF and miR‑146a‑5p had target binding sites. A luciferase reporter assay demonstrated that miR‑146a‑5p and TCSF did have complementary sequences (P<0.05). From the TCGA database, TCSF was highly expressed in lung adenocarcinoma and lung squamous cell carcinoma tissues when compared with normal lung tissues (P<0.05). Furthermore, the protein level of TCSF in cancerous lung tissues was determined by IHC, and it was concluded that TCSF protein was also upregulated in NSCLC tissues (P<0.001). A significant difference was identified following in vitro experiments for the NSCLC cell line A549, which revealed that miR‑146a‑5p and TCSF regulated cell viability, proliferation and apoptosis. In conclusion, the present study verified the target action association between TCSF and miR‑146a‑5p with high throughput data analysis and experimental results in NSCLC.

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