Circular RNA circ-LDLRAD3 serves as an oncogene to promote non-small cell lung cancer progression by upregulating SLC1A5 through sponging miR-137

RNA Biol. 2020 Dec;17(12):1811-1822. doi: 10.1080/15476286.2020.1789819. Epub 2020 Jul 13.

Abstract

Circular RNAs (circRNAs) are closely associated with the development of non-small cell lung cancer (NSCLC); however, it is still unclear whether circular RNA circ-LDLRAD3 participated in the regulation of NSCLC progression. In this study, we found that circ-LDLRAD3 was high-expressed and miR-137 was low-expressed in NSCLC tissues and cells compared to their normal counterparts, which showed negative correlations in NSCLC tissues. Further experiments validated that miR-137 could be sponged and inhibited by circ-LDLRAD3 in NSCLC cells. In addition, knock-down of circ-LDLRAD3 and miR-137 overexpression promoted NSCLC cell apoptosis, and inhibited cell proliferation and invasion. Similarly, upregulation of circ-LDLRAD3 or miR-137 ablation had opposite effects on the above cell functions. Besides, the glutamine transporter SLC1A5 was validated to be the downstream target of circ-LDLRAD3 and miR-137, and upregulated circ-LDLRAD3 increased SLC1A5 expression levels by downregulating miR-137. Furthermore, the effects of downregulated circ-LDLRAD3 on cell proliferation, apoptosis and mobility were all reversed by knocking down miR-137 and overexpressing SLC1A5. Taken together, this in vitro study found that knock-down of circ-LDLRAD3 inhibited the development of NSCLC by regulating miR-137/SLC1A5 axis.

Keywords: Non-small cell lung cancer; Slc1a5; circular RNA circ-LDLRAD3; miR-137.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Aged, 80 and over
  • Amino Acid Transport System ASC / genetics*
  • Apoptosis / genetics
  • Biomarkers, Tumor*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics*
  • Neoplasm Staging
  • Oncogenes*
  • RNA, Circular*
  • Receptors, LDL / genetics*

Substances

  • 3' Untranslated Regions
  • Amino Acid Transport System ASC
  • Biomarkers, Tumor
  • LDLRAD3 protein, human
  • MIRN137 microRNA, human
  • MicroRNAs
  • Minor Histocompatibility Antigens
  • RNA, Circular
  • Receptors, LDL
  • SLC1A5 protein, human

Grants and funding

This work was supported by the Scientific Research Projects of Shanghai Municipal Health Committee [201940102].