Long Noncoding RNA SNHG6 Promotes Proliferation and Inhibits Apoptosis in Non-small Cell Lung Cancer Cells by Regulating miR-490-3p/RSF1 Axis

Cancer Biother Radiopharm. 2020 Jun;35(5):351-361. doi: 10.1089/cbr.2019.3120. Epub 2020 Mar 23.

Abstract

Background: Nonsmall cell lung cancer (NSCLC) is a malignant cancer type and has developed into the leading cause of cancer-related death worldwide. Small nucleolar RNA host gene 6 (SNHG6) has been identified as an oncogene in multiple cancers. However, the functions of SNHG6 in tumorigenesis and progression of NSCLC are still poorly understood. Materials and Methods: The expression of SNHG6, miR-490-3p, and remodeling and spacing factor 1 (RSF1) in NSCLC tumors and cells was measured by quantitative real-time polymerase chain reaction. The correlation between miR-490-3p and SNHG6 or RSF1 was analyzed by Pearson's correlation coefficient. Luciferase reporter assay was employed for verifying the interaction between miR-490-3p and SNHG6 or RSF1. Cell viability was examined by 3-(4, 5)-dimethylthiazole-2-y1)-2, 5-biphenyl tetrazolium bromide (MTT) assay. Cell apoptosis was evaluated by flow cytometry and Western blot, respectively. Protein expression of RSF1, Bcl-2, Bax, and cleaved caspase-3 (cleaved casp-3) was detected by Western blot assay. Xenograft mice models were established by subcutaneously injecting H460 cells stably transfected with sh-SNHG6 and sh-NC. Results: SNHG6 and RSF1 expression were upregulated, whereas miR-490-3p was downregulated in NSCLC tumors and cell lines compared with normal tissues and cells. Pearson's correlation coefficient analysis indicated that miR-490-3p was correlated with SNHG6 and RSF1 inversely. Then, luciferase reporter assay confirmed the interaction between miR-490-3p and SNHG6 or RSF1. More importantly, the rescue experiments clarified that miR-490-3p inhibitor could relieve SNHG6 silencing-mediated inhibition on proliferation and promotion on apoptosis in NSCLC. In addition, the authors discovered that SNHG6 promoted cell progression by regulating miR-490-3p/RSF1 axis. However, SNHG6 knockdown hindered tumor growth in vivo by regulating RSF1 by targeting miR-490-3p. Conclusion: The authors demonstrated that SNHG6 promoted proliferation and inhibits apoptosis in NSCLC by regulating miR-490-3p/RSF1 axis, representing promising targeted therapeutic strategies against NSCLC.

Keywords: NSCLC; RSF1; SNHG6; miR-490-3p; progression.

Publication types

  • Observational Study

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung / pathology
  • Lung / surgery
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Pneumonectomy
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Trans-Activators / genetics*
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • MIRN490 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RSF1 protein, human
  • Trans-Activators
  • long non-coding RNA SNHG6, human