Targeted silencing of TEM8 suppresses non‑small cell lung cancer tumor growth via the ERK/Bcl‑2 signaling pathway

Gong,Quan; Deng,Jing; Zhang,Lijuan; Zhou,Chunyan; Fu,Chaojiang; Wang,Xicai; Zhuang,Li

doi:10.3892/mmr.2021.12234

Targeted silencing of TEM8 suppresses non‑small cell lung cancer tumor growth via the ERK/Bcl‑2 signaling pathway

Authors:
- Quan Gong
- Jing Deng
- Lijuan Zhang
- Chunyan Zhou
- Chaojiang Fu
- Xicai Wang
- Li Zhuang
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Affiliations: Department of Palliative Medicine, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China, Department of Critical Care Medicine, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China, Department of Tumor Research Institute, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China
Published online on: June 22, 2021 https://doi.org/10.3892/mmr.2021.12234
Article Number: 595
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non‑small cell lung cancer (NSCLC) is one of the most common malignancies with high rates of mortality. Although great progress has been made with the development of novel immunotherapies and targeted therapeutic strategies, the 5‑year total survival rate of lung cancer has remained unchanged over the past few decades. Therefore, more effective therapeutics are urgently needed. Tumor endothelial marker 8 (TEM8) is an integrin‑like cell surface transmembrane protein that has been demonstrated to be upregulated in numerous cancer types and previously showed promise for targeted cancer therapy. However, the role of TEM8 in NSCLC remains poorly understood. The present study aimed to investigate the effects of silencing TEM8 on expression and regulation of extracellular signal‑regulated kinase (ERK)1/2 signaling pathways in NSCLC. In the present study, a lentiviral vector that encoded a short hairpin RNA targeting TEM8 was designed and transfected into Xuanwei Lung Cancer (XWLC)‑05 lung cancer cells to silence TEM8 expression. Male BALB/c‑nu/nu mice were then given subcutaneous injections in the right dorsal flank with XWLC‑05 cells. Microvessel density was measured using an anti‑CD34 antibody. The mRNA and protein levels of ERK1/2 and Bcl‑2 in XWLC‑05 cells or xenograft tumor tissues were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. TEM8 knockdown was found to significantly inhibit tumor growth and conferred an anti‑angiogenic ability in vivo. Furthermore, TEM8 knockdown suppressed the expression of Bcl‑2 mediated by ERK1/2 activity in XWLC‑05 cells or tissues from mice with NSCLC. To conclude, these results suggest that the targeted silencing of TEM8 may serve as an effective method of treating NSCLC.

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