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Research Paper|Volume 11, Issue 18|pp 7553—7569

Long non-coding RNA TUG1 enhances chemosensitivity in non-small cell lung cancer by impairing microRNA-221-dependent PTEN inhibition

Shenghu Guo1, Lei Zhang1, Yuehua Zhang1, Zheng Wu1, Dongwei He1, Xing Li1, Zhiyu Wang1
  • 1Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P. R. China
Received: May 22, 2019Accepted: September 5, 2019Published: September 18, 2019
https://doi.org/10.18632/aging.102271

Copyright © 2019 Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Long non-coding RNA taurine up-regulated gene 1 (TUG1) emerges as new players in gene regulation in several cancers; however, its mechanism of action in non-small cell lung cancer (NSCLC) has not been well-studied. Herein, we determined expression pattern of TUG1 in NSCLC and further identified its effect on the chemosensitivity of NSCLC. Low expression of TUG1 was found in NSCLC tissues obtained from non-responders to platinum-based chemotherapy and reflected poor overall survival. TUG1 overexpression was shown to inhibit cell proliferation, migration, invasion, but facilitate apoptosis and autophagy in NSCLC cells resistant to cisplatin (DDP). Smaller size of tumor xenografts of DDP resistant NSCLC cells in the presence of TUG1 demonstrated enhancement of chemosensitivity by TUG1 in vivo. High expression of miR-221 and low expression of PTEN were determined in cancer tissues obtained from non-responders to platinum-based chemotherapy and reflected poor overall survival. TUG1 inhibited miR-221 that targeted PTEN, as evidenced by an elevated expression of PTEN in the presence of miR-221 or the absence of TUG1. Our present study reveals a model of enhancement of chemosensitivity that consists of TUG1, miR-221 and PTEN. Modulation of their levels may offer a new approach for improving anti-tumor efficacy for chemotherapeutic agents in NSCLC.