Functional Role of a Novel Long Noncoding RNA TTN-AS1 in Esophageal Squamous Cell Carcinoma Progression and Metastasis

Functional Role of a Novel Long Noncoding RNA TTN-AS1 in Esophageal Squamous Cell Carcinoma Progression and Metastasis

Functional Role of a Novel Long Noncoding RNA TTN-AS1 in Esophageal Squamous Cell Carcinoma Progression and Metastasis (#123)

Chenyu Lin ¹ , Shengnan Zhang ¹ , Ying Wang ¹ , Hanmei Xu ¹

The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province, Jiangning District, Nanjing, China

Purpose: Emerging studies demonstrate that long noncoding RNAs (lncRNA) participate in the regulation of various cancers. In the current study, a novel lncRNA-TTN-AS1 has been identiﬁed and explored in esophageal squamous cell carcinoma (ESCC).
Experimental Design: To discover a new regulatory circuitry in which RNAs crosstalk with each other, the transcriptome of lncRNA-miRNA-mRNA from ESCC and adjacent nonmalignant specimens were analyzed using multiple microarrays and diverse bioinformatics platforms. The functional role and mechanism of a novel lncRNA-TTN-AS1 were further investigated by gain-of-function and loss-of-function assays in vivo and in vitro. An ESCC biomarker panel, consisting of lncRNA-TTN-AS1, miR-133b, and FSCN1, was validated by qRT-PCR and in situ hybridization using samples from 148 patients.
Results: lncRNA-TTN-AS1 as an oncogene is highly expressed in ESCC tissues and cell lines, and promotes ESCC cell proliferation and metastasis. Mechanistically, lncRNA-TTN-AS1 promotes expression of transcription factor Snail1 by competitively binding miR-133b, resulting in the epithelial – mesenchymal transition (EMT) cascade. Moreover, lncRNA-TTN-AS1 also induces FSCN1 expression by sponging miR-133b and upregulation of mRNA-stabilizing protein HuR, which further promotes ESCC invasion cascades. We also discovered and validated a clinically applicable ESCC biomarker panel, consisting of lncRNA-TTN-AS1, miR-133b, and FSCN1, that is signi ﬁ cantly associated with overall survival and provides additional prognostic evidence for ESCC patients.
Conclusions: As a novel regulator, lncRNA-TTN-AS1 plays an important role in ESCC cell proliferation and metastasis. The lncRNA-TTN-AS1/miR133b/FSCN1 regulatory axis provides bona ﬁde targets for anti-ESCC therapies.

Authors contributing to this presentation.

Dr. Hanmei Xu Prof. of China Pharmaceutical University, Head of The Engineering Research Center of Peptide Drug Discovery and Development. Dr. Xu has been funded by the government for more than six times in recent five years, and whose research focuses on Design, screening and druggability evaluation of peptide drugs including anti-tumor, anti-rheumatoid arthritis, anti-pulmonary fibrosis and anti-acute inflammation drugs. Improvement of peptide drug effectiveness by biochemical modifications, e.g. PEGylation, fusion with IgG Fc part, connection to HSA, etc. Dr. Xu’s discoveries and efforts helped the companies to exploit four class one peptide drug. In recent five years, she published more than 70 papers, including 29 SCI papers about peptide, and applied for 39 patents of innovation, of which 15 have been authorized. As the Chair of "The 14th Chinese International Peptide Symposium & the 5th Asia-pacific International Peptide Symposium " in 2016, she successfully organized the Conference. Her group focuses on peptide-based drug and biomaterial design, in the recent five years, they undertook seven National Science and Technology Major Projects of New Drugs. The group got Science and Technology Progress Award with the work “The innovative techniques for peptide drug discovery and development” in December 2014. 80 papers were published in the last five years including 60 SCI papers. Her group applied 52 patents including 5 international patents, of which 21 have been authorized in China. The group have several joint programs with companies and the work improved the ability to discover and develop peptide drugs in China.

Functional Role of a Novel Long Noncoding RNA TTN-AS1 in Esophageal Squamous Cell Carcinoma Progression and Metastasis (#123)

Lin, C

Zhang, S

Wang, Y

Xu, H

Functional Role of a Novel Long Noncoding RNA TTN-AS1 in Esophageal Squamous Cell Carcinoma Progression and Metastasis (#123)

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Lin, C

Zhang, S

Wang, Y

Xu, H

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