SP1-mediated overexpression of lncRNA LINC01234 as a ceRNA facilitates non-small-cell lung cancer progression via regulating OTUB1

J Cell Physiol. 2019 Dec;234(12):22845-22856. doi: 10.1002/jcp.28848. Epub 2019 May 20.

Abstract

Long noncoding RNAs (lncRNAs) have been confirmed to be strongly associated with the progression of various types of cancer. LncRNA LINC01234 (LINC01234) is a newly identified tumor-related lncRNA whose upregulation has been confirmed in some tumors. However, its potential expressions and possible functions in non-small-cell lung cancer (NSCLC) have not been explored. In this study, we first found that LINC01234 expressions were distinctly upregulated in both NSCLC samples and cell lines using RT-PCR. Our group also showed that LINC01234 upregulations were modulated by nuclear transcription factor SP1. The results form clinical investigations indicated that high LINC01234 expressions were associated with positively lymph node metastasis and advanced tumor-metastasis-node (TMN) stage. Kaplan-Meier assays indicated that patients with NSCLC having high LINC01234 expressions tend to have unfavorable clinical prognosis. Using multivariate assays, it was confirmed that LINC01234 was an independent prognostic factor for patients with NSCLC. In vitro assays showed that inhibition of LINC01234 suppressed NSCLC cell proliferation, cell colony formation and metastasis, and greatly promoted apoptosis. Mechanistic investigations revealed LINC01234 promotes the progression of NSCLC cells by the modulation of miR-140 to positively regulate OTUB1 expression. Taken together our findings, they provided an exhaustive assay of LINC01234 in NSCLC and imperative clues for insights into the potential effects of lncRNAs-miRNAs regulatory network in NSCLC.

Keywords: OTUB1; lncRNA LINC01234; metastasis; miR-140; non-small-cell lung cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Binding Sites
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Cell Movement
  • Cell Proliferation
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Deubiquitinating Enzymes
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*

Substances

  • RNA, Long Noncoding
  • Sp1 Transcription Factor
  • SP1 protein, human
  • Deubiquitinating Enzymes
  • OTUB1 protein, human
  • Cysteine Endopeptidases