Hsa_circ_0039411 promotes tumorigenesis and progression of papillary thyroid cancer by miR-1179/ABCA9 and miR-1205/MTA1 signaling pathways

J Cell Physiol. 2020 Feb;235(2):1321-1329. doi: 10.1002/jcp.29048. Epub 2019 Jul 4.

Abstract

Papillary thyroid cancer (PTC) is a common malignancy in endocrine system worldwide. Increasing evidence has shown that dysregulation of circular RNAs (circRNAs) could contribute to PTC tumorigenesis. The aims of this project are to investigate the potential role and molecular mechanism of hsa_circ_0039411 in PTC. In the project, RT-qPCR was performed to measure the expression profile of hsa_circ_0039411 in PTC tissues and cells. Cell counting kit-8, clonogenic, flow cytometric, and transwell experiments were used to identify the biological role of hsa_circ_0039411 on PTC cell progression. Bioinformatics methods, along with the dual-luciferase reporter test, was used to identify the potential mechanism of hsa_circ_0039411. Hsa_circ_0039411 was identified as enhanced in PTC tissues/cells. Gain-of-function experiments indicated that hsa_circ_0039411 facilitated PTC cell growth, migration, and invasion and inhibited cell apoptosis. Knockdown of hsa_circ_0039411 caused the opposite effects mentioned above. The mechanism exploration showed that hsa_circ_0039411 functioned as a sponge for miR-1179 and miR-1205 to elevate ATP-binding cassette transporter A9 (ABCA9) and metastasis-associated 1 (MTA1) expression at the post-transcriptional level, respectively. Further investigation confirmed that the functions of hsa_circ_0039411 are dependent on its modulation of ABCA9 and MTA1 in PTC cells. This study uncovered a mechanism of hsa_circ_0039411 in PTC, which might act as a novel therapeutic target for PTC.

Keywords: ATP-binding cassette transporter A9; circular RNA; hsa_circ_0039411; metastasis-associated 1; miR-1179; miR-1205; papillary thyroid cancer.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Carcinogenesis / genetics*
  • Disease Progression
  • Humans
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Repressor Proteins / genetics
  • Signal Transduction / genetics
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • Trans-Activators / genetics

Substances

  • ABCA9 protein, human
  • ATP-Binding Cassette Transporters
  • MIRN1179 microRNA, human
  • MIRN1205 microRNA, human
  • MicroRNAs
  • MTA1 protein, human
  • RNA, Circular
  • Repressor Proteins
  • Trans-Activators