A long non-coding RNA LNBC3 facilitates non-small cell lung cancer progression by stabilizing BCL6

J Clin Lab Anal. 2020 Apr;34(4):e23122. doi: 10.1002/jcla.23122. Epub 2019 Nov 19.

Abstract

Background: The non-small cell lung cancer (NSCLC) is a common malignancy worldwide. Numerous reports have shown the critical role of long non-coding RNAs (lncRNAs) in NSCLC. However, the role of a novel lncRNA named LNBC3 is still unknown.

Methods: By lncRNA profiling, novel lncRNAs related to NSCLC were identified. LNBC3 expression was quantified by qRT-PCR. Migration and viability assays were performed to evaluate the function of LNBC3 in vitro. In vivo xenograft model was conducted to determine the oncogenic functions of LNBC3. RNA immunoprecipitation (RIP) followed by mass spectrometry (MS) was utilized to identify BCL6 as LNBC3 binding target.

Results: LNBC3 is markedly overexpressed in tumor tissues and NSCLC cell lines. Higher LNBC3 levels correlated with advanced TNM stages, larger tumor size, and metastasis. LNBC3 promoted NSCLC migration and viability. The in vivo experiments demonstrated that xenograft tumor growth and proliferation were facilitated with increasing LNBC3 levels. The antisense oligonucleotides (ASOs) targeting LNBC3 substantially inhibited lung cancer progression. Mechanistic studies showed that LNBC3 could interact with BCL6 leading to BCL6 stabilization through reduced proteasomal degradation.

Conclusions: Collectively, our data have identified a novel lncRNA LNBC3 in NSCLC progression. The LNBC3-BCL6 axis might be a potential target for pharmaceutical intervention.

Keywords: B-cell lymphoma 6; BCL6 on chromosome 3; antisense oligonucleotides; non-small cell lung cancer.

MeSH terms

  • A549 Cells
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice, Nude
  • Oligonucleotides, Antisense / genetics
  • Proto-Oncogene Proteins c-bcl-6 / genetics*
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • RNA, Long Noncoding / genetics*
  • Ubiquitination
  • Xenograft Model Antitumor Assays

Substances

  • BCL6 protein, human
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Long Noncoding