LncRNA SBF2-AS1 affects the radiosensitivity of non-small cell lung cancer via modulating microRNA-302a/MBNL3 axis

Cell Cycle. 2020 Feb;19(3):300-316. doi: 10.1080/15384101.2019.1708016. Epub 2020 Jan 13.

Abstract

Background: Long non-coding RNAs (lncRNAs) have been reported to participate in many diseases including non-small cell lung cancer (NSCLC), thus our objective was to investigate the impact of lncRNA SBF2-AS1 modulating microRNA-302a (miR-302a) expression on radiosensitivity of NSCLC.Methods: The expression of SBF2-AS1, miR-302a and muscleblind-like 3 (MBNL3) in NSCLC tissues of the radiotherapy-sensitive and radiotherapy-resistant groups was tested. The radiosensitivity of parent and resistant strains (NCI-H1299 and NCI-H1299R cells) was detected. Further, cells were treated with si-SBF2-AS1 and miR-302a mimics to determine their roles in proliferation and apoptosis of parent strain and resistant strain cells as well as transfected cells. The in-vivo growth capacity of the cells and the effect of radiotherapy on tumor size of NSCLC were detected.Results: Up-regulated SBF2-AS1 and MBNL3 and down-regulated miR-302a in NSCLC tissues of the radiotherapy resistant group. Overexpression of SBF2-AS1 and MBNL3 and low expression of miR-302a were witnessed in NCI-H1299R cells. Down-regulated SBF2-AS1 or up-regulated miR-302a suppressed the proliferation while boosted the apoptosis of NCI-H1299 cells and decreased the radioresistance of the NCI-H1299R cells. Silencing SBF2-AS1 or up-regulating miR-302a restrained tumor growth in vivo.Conclusion: Our study presents that high expression of miR-302a or inhibition of SBF2-AS1 can enhance the radiosensitivity and apoptosis of NSCLC cells through downregulation of MBNL3, which is a therapeutic target for NSCLC.

Keywords: Apoptosis; LncRNA SBF2-AS1; MicroRNA-302a; Muscleblind-like 3; Non-small cell lung cancer; Proliferation; Radiosensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / radiation effects*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Cell Line, Tumor
  • Cell Proliferation / radiation effects
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Radiation Tolerance
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • MBNL3 protein, human
  • MIRN302A microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • long non-coding RNA SBF2-AS1, human

Grants and funding

This study was supported by General Program of Natural Science Foundation of Liaoning Province(2015020464), Major Science and Technology Platform of Liaoning Higher Institution (No.2916009), Science Research Foundation for Absorbed Talents Program of Liaoning Cancer Hospital and Special Project of Applied Technology of Population and Health by Shenyang Science and Technology Plan (No.18-014-4-04); General Program of Natural Science Foundation of Liaoning Province [2015020464];Science Research Foundation for Absorbed Talents Program of Liaoning Cancer Hospital and Special Project of Applied Technology of Population and Health by Shenyang Science and Technology Plan [18-014-4-04]; Major Science and Technology Platform of Liaoning Higher Institution [2916009].