LncRNA SNHG1 contributes to the cisplatin resistance and progression of NSCLC via miR-330-5p/DCLK1 axis

Exp Mol Pathol. 2021 Jun:120:104633. doi: 10.1016/j.yexmp.2021.104633. Epub 2021 Mar 19.

Abstract

Background: Long non-coding RNAs (lncRNAs) are involved in the occurrence and progression of multiple cancers, including non-small cell lung cancer (NSCLC). Herein, we explored the exact role and underlying mechanism of lncRNA small nucleolar RNA host gene 1 (SNHG1) in NSCLC.

Methods: The levels of SNHG1, microRNA-330-5p (miR-330-5p) and doublecortin-like kinase 1 (DCLK1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to measure the chemoresistance and proliferation of NSCLC cells. The metastasis and apoptosis of NSCLC cells were examined by transwell migration and invasion assays and flow cytometry. Western blot assay was conducted to detect the levels of proliferation-associated proteins and DCLK1. The interaction between miR-330-5p and SNHG1 or DCLK1 was predicted by StarBase and microT_CDS databases. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to validate these interactions. In vivo chemosensitivity experiment was conducted to assess the function of SNHG1 in the chemoresistance of NSCLC in vivo.

Results: SNHG1 was dramatically up-regulated in cisplatin (DDP)-resistant NSCLC tissues and cells. SNHG1 promoted the DDP resistance and malignant behaviors of NSCLC cells. SNHG1 functioned through targeting miR-330-5p, and si-SNHG1-mediated effects in NSCLC cells were attenuated by the addition of in-miR-330-5p. DCLK1 messenger RNA (mRNA) could directly bind to miR-330-5p, and miR-330-5p acted as a tumor suppressor in NSCLC through down-regulating DCLK1. SNHG1 silencing elevated the DDP sensitivity of NSCLC cells in vivo.

Conclusion: SNHG1 elevated DDP resistance and malignant potential of NSCLC cells through elevating the level of DCLK1 via sponging miR-330-5p.

Keywords: Chemoresistance; Cisplatin; DCLK1; NSCLC; SNHG1; miR-330-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Movement
  • Cell Proliferation
  • Cisplatin / pharmacology*
  • Doublecortin-Like Kinases
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Long Noncoding / genetics*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MIRN330 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA SNHG1, human
  • DCLK1 protein, human
  • Doublecortin-Like Kinases
  • Protein Serine-Threonine Kinases
  • Cisplatin