Overexpression of FAM83H-AS1 indicates poor patient survival and knockdown impairs cell proliferation and invasion via MET/EGFR signaling in lung cancer

Sci Rep. 2017 Feb 15:7:42819. doi: 10.1038/srep42819.

Abstract

Whole transcriptome analyses of next generation RNA sequencing (RNA-Seq) data from human cancer samples reveled thousands of uncharacterized non-coding RNAs including long non-coding RNA (lncRNA). Recent studies indicated that lncRNAs are emerging as crucial regulators in cancer processes and potentially useful as biomarkers for cancer diagnosis and prognosis. To delineate dysregulated lncRNAs in lung cancer, we analyzed RNA-Seq data from 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues. FAM83H-AS1, one of the top dysregulated lncRNAs, was found to be overexpressed in tumors relative to normal lung and significantly associated with worse patient survival in LUAD. We verified this diagnostic/prognostic potential in an independent cohort of LUAD by qRT-PCR. Cell proliferation, migration and invasion were decreased after FAM83H-AS1 knockdown using siRNAs in lung cancer cells. Flow cytometry analysis indicated the cell cycle was arrested at the G2 phase after FAM83H-AS1 knockdown. Mechanistically, we found that MET/EGFR signaling was regulated by FAM83H-AS1. Our study indicated that FAM83H-AS1 plays an important role in lung tumor progression and may be potentially used as diagnostic/prognostic marker. Further characterization of this lncRNA may provide a novel therapeutic target impacting MET/EGFR signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Neoplasm Invasiveness
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism
  • RNA, Long Noncoding / genetics*
  • Sequence Analysis, RNA
  • Signal Transduction*
  • Survival Analysis
  • Up-Regulation*

Substances

  • RNA, Long Noncoding
  • onco-lncRNA-3, human
  • EGFR protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met