LINC01410/ miR-3619-5p/ FOXM1 Feedback Loop Regulates Papillary Thyroid Carcinoma Cell Proliferation and Apoptosis

Cancer Biother Radiopharm. 2019 Nov;34(9):572-580. doi: 10.1089/cbr.2019.2854. Epub 2019 Oct 23.

Abstract

Backgrounds: Thyroid cancer (TC) is a prevalent type of cancer in endocrine system. Past decades have seen the rising mortality and morbidity of TC. Long noncoding RNAs are renowned modulators of cancer onset and progression as validated by mounting studies. Long intergenic non-protein coding RNA 1410 (LINC01410) has been suggested as tumor-promoting gene in colon cancer and gastric cancer, but its role in TC is elusive. This study investigated the impact and mechanism of LINC01410 in TC. Materials and Methods: RT-qPCR and western blot were used to detect gene expression levels. Cell counting kit-8 (CCK-8) and ethynyl-2'-deoxyuridine (EdU) assays were used to determine proliferation. Caspase-3 activity assay was used to examine apoptosis. Intermolecular interaction was investigated by luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. Results: We confirmed the elevation of LINC01410 expression in TC cells. Loss-of-function experiments indicated that LINC01410 knockdown suppressed proliferation and facilitated apoptosis in TC. Mechanism research illustrated that LINC01410 positively regulated forkhead box M1 (FOXM1) expression through targeting miR-3619-5p, and that FOXM1 in turn transcriptionally activated LINC01410. Rescue experiments validated that LINC01410 regulated TC proliferation and apoptosis through miR-3619-5p/FOXM1. Conclusions: This study demonstrated that LINC01410/miR-3619-5p/FOXM1 positive feedback loop regulated cell proliferation and apoptosis in TC, shedding a light on the molecular target identification and promising treatment improvement in TC.

Keywords: FOXM1; LINC01410; miR-3619-5p; papillary thyroid carcinoma.

MeSH terms

  • Apoptosis / genetics*
  • Binding Sites
  • Cell Line
  • Cell Proliferation / genetics*
  • Forkhead Box Protein M1 / genetics*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Mutation
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • MIRN-3619 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding