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

Aging (Albany NY). 2020 Nov 4;12(21):21904-21922. doi: 10.18632/aging.104011. Epub 2020 Nov 4.

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.

Keywords: LINC00968; SMAD7; lung adenocarcinoma (LUAD); metastasis; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / secondary
  • Animals
  • Cell Movement
  • Cell Proliferation
  • Databases, Genetic
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Smad7 Protein / metabolism*
  • Tumor Burden

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SMAD7 protein, human
  • Smad7 Protein