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Research Paper|Volume 12, Issue 21|pp 21904—21922

LINC00968 can inhibit the progression of lung adenocarcinoma through the miR-21-5p/SMAD7 signal axis

Yuxing Zhu1, Hao Bo1,2, Zhizhao Chen1,3, Jingjing Li1,3, Dong He4, Mengqing Xiao1, Liang Xiang1, Long Jin1, Jianda Zhou5, Lian Gong1, Yanhong Zhou6, Ming Zhou6, Wei Xiong6, Xiaowei Xing7, Ruhong Li8, Ke Cao1
  • 1Department of Oncology, Third Xiangya Hospital of Central South University, Changsha 410013, China
  • 2Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
  • 3Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha 410083, Hunan, China
  • 4Department of Respiration, The Second People’s Hospital of Hunan Province of Hunan University of Chinese Medicine, Changsha 410000, China
  • 5Department of Plastic Surgery, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China
  • 6Cancer Research Institute and Key Laboratory of Carcinogenesis of Ministry of Health, Central South University, Changsha 410078, China
  • 7Center for Medical Experiments, Third Xiangya Hospital, Central South University, Changsha 410013, China
  • 8Yan’an Affiliated Hospital of Kunming Medical University, Kunming 650051, China
* Equal contribution
Received: December 17, 2019Accepted: July 30, 2020Published: November 4, 2020
https://doi.org/10.18632/aging.104011

Copyright: © 2020 Li 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

Background: Long non-coding RNAs (LncRNAs) have been associated with several types of cancer. However, little is known about their role in lung adenocarcinoma (LUAD).

Results: LINC00968 was significantly differentially expressed in LUAD tissues. Downregulated LINC00968 was associated with clinicopathological features of LUAD. LINC00968 inhibited cell growth and metastasis by regulating the Hippo signaling pathway We demonstrated that LINC00968 acts as a ceRNA to consume miR-21-5p, enhancing the accumulation of SMAD7, a miR-21-5p target.

Conclusions: LINC00968 limits LUAD progression via the miR-21-5p/SMAD7 axis and may serve as a prognostic biomarker and therapeutic target for LUAD.

Methods: We conducted comprehensive data mining on LINC00968 based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. The expression of LINC00968 in LUAD cells was determined using in situ hybridization. We detected LINC00968 function in LUAD cells using the MTT, clone formation, and transwell assays, and tumor xenografts. Label-free quantitative proteomics, western blotting, a dual-luciferase reporter assay, immunofluorescence, and RNA immunoprecipitation assays were used to determine the correlations among LINC00968, miR-21-5p, and SMAD7. Gain- and loss-function approaches were used to explore the effects of LINC00968, miR-21-5p, and SMAD7 on cell proliferation, migration, and invasion.