The role and potential mechanisms of LncRNA-TATDN1 on metastasis and invasion of non-small cell lung cancer.

Niu Zequn,Meng Xia,Deng Wenjing,Hou Yanli,Ming Zongjuan,Yang Shuanying,Wang Wei,Zhang Yuping,Li Wei,Zhang Xuemei,Zhong Yujie,Fan Na

doi:10.18632/oncotarget.7788

Niu Zequn, Meng Xia + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.7788

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Abstract

The invasion and metastasis of malignant tumor cells lead to normal tissue destruction and are major prognostic factors for many malignant cancers. Long non-coding RNA (LncRNA) is associated with occurrence, development and prognoses of non-small cell lung cancer (NSCLC), but its mechanisms of action involved in tumor invasion and metastasis are not clear. In this study, we screened and detected the expression of LncRNA in two NSCLC lines 95D and 95C by using high throughput LncRNA chip. We found that TATDN1 (Homo sapiens TatD DNase domain containing 1, TATDN1), one of LncRNAs, was highly expressed in 95D cells and NSCLC tumor tissues compared to 95C cells. Knockdown of TATDN1–1 by shRNA significantly inhibited cell proliferation, adhesion, migration and invasion in 95D cells. Further mechanism study showed that TATDN1 knockdown suppressed the expression of E-cadherin, HER2, β-catenin and Ezrin. Moreover, knockdown TATDN1 also inhibited tumor growth and metastasis in a 95D mouse model in vivo by inhibiting β-catenin and Ezrin. These data indicate that TATDN1 expression is associated with 95D cells' higher potential of invasion and metastasis, and suggest that TATDN1 may be a potential prognostic factor and therapeutic target for NSCLCs.

Highlights

Lung cancer was the most commonly diagnosed cancer as well as the leading cause of cancer death, with 1.4 million deaths worldwide annually [1]
Long non-coding RNA (LncRNA) TATDN1 was highly expressed in non-small cell lung cancer (NSCLC) 95D cells
When the 95D cell line was transfected with the lentivirus expressing TATDN1 small interfering RNA (siRNA), the LncRNA TATDN1 was significantly blocked by the siRNAs and the silencing effect from the siRNA targeting at the site 3 is most significant (Figure 1F)

Summary

Introduction

Lung cancer was the most commonly diagnosed cancer as well as the leading cause of cancer death, with 1.4 million deaths worldwide annually [1]. Almost 80% of lung cancers are non-small cell lung cancer (NSCLC) [2]. Lung cancer surpassed breast cancer as the leading cause of cancer death in women and is expected to account for 26% of all female cancer deaths [3]. The prognosis for NSCLC is still dismal, and the overall 5-year survival is only 15% [4]. Treatment failure and death of the patients with NSCLC are correlated with high potential for invasion and metastasis.

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