Research Papers:

TLR4/ROS/miRNA-21 pathway underlies lipopolysaccharide instructed primary tumor outgrowth in lung cancer patients

Xianqi Zhang, Chunhong Wang, Shan Shan, Xiyu Liu, Zhongmin Jiang and Tao Ren _

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Oncotarget. 2016; 7:42172-42182. https://doi.org/10.18632/oncotarget.9902

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Xianqi Zhang1,*, Chunhong Wang2,*, Shan Shan2, Xiyu Liu3, Zhongmin Jiang1, Tao Ren2

1Department of Thoracic Surgery, Qianfoshan Hospital, Shandong University, Shandong 250014, China

2Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

3Department of Thoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, China

*These authors contributed equally to this work

Correspondence to:

Tao Ren, email: rentaosh@126.com

Zhongmin Jiang, email: qyjzm@sina.com

Keywords: lung cancer, LPS, TLR4, miR-21, ROS

Received: March 21, 2016     Accepted: May 16, 2016     Published: June 07, 2016


Activation of Toll-like receptor 4 (TLR4) signaling in human lung cancer with lipopolysaccharide (LPS) enhances tumor progression. However, whether primary human lung cancer outgrowth could respond to LPS and underlying mechanisms are unclear. Here we determined that TLR4 activation with LPS promoted outgrowth of primary human lung cancer cells in vitro and in vivo. Mechanistically, LPS stimulation increased expression levels of microRNA-21 (miR-21) in primary human lung cancer cells. Inhibition of miR-21 blocked the enhanced lung cancer growth induced by LPS in vitro and in vivo. Up-regulation of miR-21 promoted outgrowth of primary human lung cancer. Down-regulation of miR-21 limited primary human lung cancer outgrowth. Further, TLR4 activation in primary human lung cancer cells increased their ROS levels. Scavenge of ROS abrogated the up-regulation of miR-21 in primary human lung cancer cells and attenuated LPS-induced outgrowth. For in vivo relevance, expression of TLR4 was correlated with miR-21 expression and ROS production in freshly isolated, untreated primary human lung cancer cells. These findings demonstrate an essential role of TLR4/ROS/miR-21 pathway in LPS-induced outgrowth of primary human lung cancer. Our study connected a framework of innate signaling, oxidative stress and microRNA in tumor immunity and provided clues for developing new therapeutics for lung cancer.

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