CircRNA NRIP1 promotes papillary thyroid carcinoma progression by sponging mir-195-5p and modulating the P38 MAPK and JAK/STAT pathways

Diagn Pathol. 2021 Oct 25;16(1):93. doi: 10.1186/s13000-021-01153-9.

Abstract

Background: Circular RNAs (circRNAs) have become a hot topic in the area of tumor biology due to its closed structure and the post-transcriptional regulatory effect. This study aims to clarify the roles of circRNA nuclear receptor-interacting protein 1 (NRIP1; circNRIP1) and the possible mechanisms in papillary thyroid carcinoma (PTC).

Methods: The real-time PCR was used to detect the expression level of CircRNA NRIP1 in PTC specimens and cell lines. The effects of CircRNA NRIP1 and miR-195-5p on the PTC cell functions were detected by MTT, transwell, and flow cytometry assays. Dual-luciferase reporter assays and pull down assays were used to verify the association between circRNA NRIP1 and miR-195-5p. The murine xenograft models were constructed to detect the roles of CircRNA NRIP1 and miR-195-5p. Western blot was applied to detect the effects of CircRNA NRIP1 and miR-195-5p on the P38 MAPK and JAK/STAT singling pathways.

Results: CircRNA NRIP1 was over-expressed in PTC tissues and cells and the high levels of CircRNA NRIP1 were correlated with advanced PTC stage. Depletion of CircRNA NRIP1 inhibited PTC cell proliferation, invasion, while accelerated apoptosis. miR-195-5p upregulation repressed proliferation and invasion capabilities, and accelerated apoptosis of PTC cell lines and restraining the growth of tumor xenografts, while the functions were reversed following CircRNA NRIP1 overexpression in PTC cells and tumor xenografts. Besides, the protein levels of p-p38, p-JAK2 and p-STAT1 were remarkably down-regulated in miR-195-5p overexpressed PTC cells and tumor xenografts, whereas CircRNA NRIP1 up-regulation overturned the impacts.

Conclusions: In conclusion, CircRNA NRIP1 promoted PTC progression by accelerating PTC cells proliferation, invasion and tumor growth, while impeding apoptosis by way of sponging miR-195-5p and regulating the P38 MAPK and JAK/STAT pathways.

Keywords: CircRNA NRIP1; JAK/STAT pathway; P38 MAPK pathway; Papillary thyroid carcinoma; miR-195-5p.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Janus Kinase 2 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Phosphorylation
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • STAT1 Transcription Factor / metabolism*
  • Signal Transduction
  • Thyroid Cancer, Papillary / enzymology*
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms / enzymology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology
  • Tumor Burden
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • MIRN195 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • JAK2 protein, human
  • Janus Kinase 2
  • p38 Mitogen-Activated Protein Kinases