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Onco Targets Ther. 2021 Aug 10;14:4415-4426. doi: 10.2147/OTT.S297336. eCollection 2021.

Long Non-Coding RNA TRG-AS1 Promoted Proliferation and Invasion of Lung Cancer Cells Through the miR-224-5p/SMAD4 Axis.

OncoTargets and therapy

Mengyan Zhang, Weiguo Zhu, Mansour Haeryfar, Sumei Jiang, Xiang Jiang, Wei Chen, Jiancheng Li

Affiliations

  1. The School of Clinical Medicine, Fujian Medical University, Fuzhou, People's Republic of China.
  2. Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, 350014, People's Republic of China.
  3. Department of Radiotherapy, The Affiliated Huaian No.1 People' s Hospital of Nanjing Medical University, Huaian, Jiangsu Province, 223300, People's Republic of China.
  4. Department of Microbiology and Immunology, Western University, London, Ontario, N6A 3K7, Canada.
  5. Department of B-ultrasound, The Affiliated Huaian No.1 People' s Hospital of Nanjing Medical University, Huaian, Jiangsu Province, 223300, People's Republic of China.
  6. Department of Hernia Surgery, The Affiliated Huaian No.1 People' s Hospital of Nanjing Medical University, Huaian, Jiangsu Province, 223300, People's Republic of China.
  7. Department of Respiratory Medicine, The Affiliated Huaian No.1 People' s Hospital of Nanjing Medical University, Huaian, Jiangsu Province, 223300, People's Republic of China.

PMID: 34408438 PMCID: PMC8364376 DOI: 10.2147/OTT.S297336

Abstract

INTRODUCTION: The aim of this study was to investigate the role and mechanism of long non-coding RNA (lncRNA) TRG-AS1 in mediating the proliferation, invasion and migration of lung cancer cells as well lung tumor growth.

METHODS: Firstly, the expression levels of TRG-AS1, miR-224-5p in lung cancer tissues or cells were quantified by quantitative real-time PCR. Western blot analysis was conducted to measure the expression levels of protein SMAD4. CCK-8 assay, wound healing assay and transwell assay were conducted to evaluate cell proliferation, migration and invasion, respectively. The interaction between TRG-AS1 and miR-224-5p was predicted by bioinformatics analysis. Dual-luciferase assay and RNA pull-down assay were performed to further confirm their interaction. In addition, the interaction between miR-224-5p and SMAD4 was detected by RIP assay.

RESULTS: The results showed that TRG-AS1 was highly upregulated and miR-224-5p was downregulated in lung cancer. A negative correlation was found between TRG-AS1 and miR-224-5p. Furthermore, upregulation of TRG-AS1 promoted cell proliferation and invasion, while overexpression of miR-224-5p attenuated the effects of TRG-AS1. The downstream protein SMAD4 played an important role. In vivo study showed that knockdown of TRG-AS1 effectively retarded tumor growth.

DISCUSSION: Our data suggested that the TRG-AS1/miR-224-5p/SMAD4 axis may be a potential therapeutic target in lung cancer.

© 2021 Zhang et al.

Keywords: TRG-AS1; lung cancer; miR-224-5p/SMAD4 axis; therapeutic target

Conflict of interest statement

The authors report no conflicts of interest in this work.

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