The TGFβ-induced lncRNA TBILA promotes non-small cell lung cancer progression in vitro and in vivo via cis-regulating HGAL and activating S100A7/JAB1 signaling

Zhiliang Lu; Yuan Li; Yun Che; Jianbing Huang; Shouguo Sun; Shuangshuang Mao; Yuanyuan Lei; Ning Li; Nan Sun; Jie He

doi:10.1016/j.canlet.2018.06.013

The TGFβ-induced lncRNA TBILA promotes non-small cell lung cancer progression in vitro and in vivo via cis-regulating HGAL and activating S100A7/JAB1 signaling

Cancer Lett. 2018 Sep 28:432:156-168. doi: 10.1016/j.canlet.2018.06.013. Epub 2018 Jun 15.

Authors

Zhiliang Lu¹, Yuan Li¹, Yun Che¹, Jianbing Huang¹, Shouguo Sun¹, Shuangshuang Mao¹, Yuanyuan Lei¹, Ning Li¹, Nan Sun², Jie He³

Affiliations

¹ Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
² Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address: sunnan@vip.126.com.
³ Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address: prof.jiehe@gmail.com.

PMID: 29908210
DOI: 10.1016/j.canlet.2018.06.013

Abstract

Long non-coding RNAs (lncRNAs) play critical roles in multiple cellular processes in non-small cell lung cancer (NSCLC); however, the involvement of lncRNAs in the transforming growth factor-beta (TGFβ) signaling pathway, the critical tumor cell epithelial-mesenchymal transition (EMT) and metastasis pathway, remains poorly understood. To address this issue, we compared the lncRNAs expression patterns of NSCLC cells treated with and without TGFβ1 treatment. We observed that one of the most prominent hits, TGFβ-induced lncRNA (TBILA), promoted NSCLC progression and was upregulated in tumor tissues. Upregulated TBILA promotes human germinal center-associated lymphoma (HGAL) expression by binding to the Smad transcription factor complex, thereby enhancing RhoA activation. In addition, TBILA induces the S100A7-c-Jun activation domain-binding protein 1 (JAB1) pathway by binding to nuclear S100A7 and enhances pro-survival pathways in NSCLC. These findings have provided us with a new perspective regarding the regulation of the TGFβ signaling pathway in NSCLC and suggest that the lncRNA TBILA can serve as a target for anticancer therapies.

Keywords: Metastasis; NSCLC; TBILA; TGFβ; lncRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
COP9 Signalosome Complex / genetics
COP9 Signalosome Complex / metabolism*
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / pathology*
Case-Control Studies
Cell Movement
Cell Proliferation
Disease Progression
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Humans
In Vitro Techniques
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics
Lung Neoplasms / metabolism
Lung Neoplasms / pathology*
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
Mice, Nude
Mice, SCID
Microfilament Proteins / genetics
Microfilament Proteins / metabolism*
Peptide Hydrolases / genetics
Peptide Hydrolases / metabolism*
RNA, Long Noncoding / genetics*
S100 Calcium Binding Protein A7 / genetics
S100 Calcium Binding Protein A7 / metabolism*
Signal Transduction
Transforming Growth Factor beta1 / pharmacology*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

GCSAM protein, human
Intracellular Signaling Peptides and Proteins
Microfilament Proteins
RNA, Long Noncoding
S100 Calcium Binding Protein A7
S100A7 protein, human
TGFB1 protein, human
Transforming Growth Factor beta1
Peptide Hydrolases
COPS5 protein, human
COP9 Signalosome Complex