Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts

Bioengineered. 2019 Dec;10(1):425-436. doi: 10.1080/21655979.2019.1669518.

Abstract

Stromal interaction molecule 1 (STIM1) is a calcium-sensing protein localized in the membrane of the endoplasmic reticulum. The expression of STIM1 has been shown to be closely associated with cell proliferation. The aim of the present study was to investigate the role of STIM1 in the regulation of cancer progression and its clinical relevance. The data demonstrated that the expression of the STIM1 was significantly higher in non-small-cell lung cancer (NSCLC) tissues than in benign lesions and was associated with advanced NSCLC T stage. Knockdown of STIM1 expression in NSCLC cell lines A549 and SK-MES-1 significantly inhibited cell proliferation and induces A549 and SK-MES-1 cell arrest at the G2/M and S phases of the cell cycle. Western blotting showed that the expression of cyclin-dependent kinase (CDK) 1 and CDK2 were reduced while knockdown of STIM1 expression. Furthermore, knockdown of STIM1 in NSCLC cells significantly reduced the levels of xenograft tumor growth in nude mice. These data indicate that aberrant expression of the STIM1 protein may contribute to NSCLC progression. Future studies should focus on targeting STIM1 as a novel strategy for NSCLC therapy.

Keywords: Non-small-cell lung cancer; cell cycle; immunohistochemistry; proliferation; stromal interaction molecule 1.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology
  • Adolescent
  • Adult
  • Aged
  • Animals
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Stromal Interaction Molecule 1 / antagonists & inhibitors
  • Stromal Interaction Molecule 1 / genetics*
  • Stromal Interaction Molecule 1 / metabolism
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Neoplasm Proteins
  • RNA, Small Interfering
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2

Grants and funding

This work was supported in part by grants from National Natural Science Foundation of China (#816025029, #81660389 and #81760423), the Yunnan Provincial General Program for Applied Basic Research (#2017FE468, #2017FB126 and #2018FB138), Yunnan Provincial Science and Technology Bureau (#2017HC006).