SOX2-induced upregulation of lncRNA LINC01561 promotes non-small-cell lung carcinoma progression by sponging miR-760 to modulate SHCBP1 expression

J Cell Physiol. 2020 Oct;235(10):6684-6696. doi: 10.1002/jcp.29564. Epub 2020 Jan 31.

Abstract

Long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in tumorigenesis. lncRNA LINC01561 (LINC01561) is a newly identified tumor-related lncRNA and its dysregulation has been demonstrated in several tumors. However, whether LINC01561 is involved in the progression of non-small-cell lung carcinoma (NSCLC) and its underlying mechanisms remain unknown. In this study, we first provided evidence that LINC01561 expressions were distinctly upregulated in NSCLC tissues and cell lines. Combining with bioinformatics assays and mechanism experiments, our group demonstrated that LINC01561 was activated by SOX2 in NSCLC. Clinical research revealed that upregulation of LINC01561 was related to poorer clinicopathologic features and shorter survival time. Functionally, suppression of LINC01561 exhibited tumor-suppressive functions through impairing cell proliferation, migration, and invasion as well as inducing apoptosis. Moreover, we verified that LINC01561 could directly bind to miR-760, isolating miR-760 from its target gene SHC SH2 domain-binding protein 1 (SHCBP1). We also found that SHCBP1 was lowly expressed in NSCLC and served as a tumor promoter. A functional study indicated that LINC01561 regulated SHCBP1 expression by competitively binding to miR-760. In summary, our findings indicated that SOX2-induced overexpression of LINC01561 promoted the proliferation and metastasis by acting as a competing endogenous RNA to modulate SHCBP1 by sponging miR-760.

Keywords: LINC01561; NSCLC; SHCBP1; SOX2; metastasis; miR-760; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Long Noncoding / genetics*
  • SOXB1 Transcription Factors / genetics*
  • Shc Signaling Adaptor Proteins / genetics*
  • Signal Transduction / genetics
  • Up-Regulation / genetics*

Substances

  • MIRN760 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SHCBP1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Shc Signaling Adaptor Proteins